Clinical pharmacokinetics of vancomycin in the neonate: a review

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In this case, the immune system and healing continue to be mutually dependent and are presented in relation to the bidirectional immune profile and psychological profile of the patient because large lesions cause anxiety and stress, and these effects directly affect healing and inflammatory capacity. Finally, BZD compounds are ultimately responsible for alterations in healing and tissue regeneration." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Flavia Egydio, Gabriel Natan Pires, Sergio Tufik, Monica Levy Andersen" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Flavia" "apellidos" => "Egydio" ] 1 => array:2 [ "nombre" => "Gabriel Natan" "apellidos" => "Pires" ] 2 => array:2 [ "nombre" => "Sergio" "apellidos" => "Tufik" ] 3 => array:2 [ "nombre" => "Monica Levy" "apellidos" => "Andersen" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222017793?idApp=UINPBA00004N" "url" => "/18075932/0000006700000007/v1_202212011706/S1807593222017793/v1_202212011706/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "REVIEW" "titulo" => "Clinical pharmacokinetics of vancomycin in the neonate: a review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "831" "paginaFinal" => "837" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Gian Maria Pacifici, Karel Allegaert" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Gian Maria" "apellidos" => "Pacifici" "email" => array:1 [ 0 => "pacifici@biomed.unipi.it" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "I" "identificador" => "af1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "c1" ] ] ] 1 => array:3 [ "nombre" => "Karel" "apellidos" => "Allegaert" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "af2" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "University of Pisa, Medical School, Department of Neurosciences, Section of Pharmacology, Pisa/IT" "etiqueta" => "I" "identificador" => "af1" ] 1 => array:3 [ "entidad" => "Neonatal Intensive Care Unit, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium" "etiqueta" => "II" "identificador" => "af2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "c1" "etiqueta" => "*" "correspondencia" => "Tel.: 39 050-2218721" ] ] ] ] "textoCompleto" => "INTRODUCTIONNeonates have a higher risk of nosocomial infections due to humoral, cellular and myeloid cell functions combined with the use of invasive techniques (e.g., central venous catheter and endotracheal intubation) (<a class="elsevierStyleCrossRef" href="#bib1">1</a>). Because neonatal bacterial sepsis has mortality rates of 10-20% and causes morbidity in 25-30% of survivors (<a class="elsevierStyleCrossRef" href="#bib2">2</a>,<a class="elsevierStyleCrossRef" href="#bib3">3</a>), effective and tolerated anti-microbiologic treatment regimens are required. Coagulase-negative Staphylococci and Staphylococcus aureus are common nosocomial bacterial pathogens, and vancomycin is the first-choice antibiotic to treat these pathogens, especially in methicillin-resistance settings (<a class="elsevierStyleCrossRef" href="#bib4">4</a>). Vancomycin is active against gram-positive bacteria. Staphylococcus epidermis, including methicillin-resistant strains, are inhibited by vancomycin concentrations of 1-4 µg/ml. Staphylococcus pyogenes, Streptococcus pneumonia, and Streptococcus viridans are susceptible to 2 µg/ml vancomycin. Bacillus spp. are inhibited by 2 µg/ml, Corynebacterium spp. by 0.04-3.1 µg/ml and Clostridium spp. by 0.39-6 µg/ml vancomycin (<a class="elsevierStyleCrossRef" href="#bib5">5</a>). Peak and trough concentrations of vancomycin should be <40 μg/ml and <10 μg/ml, respectively, to both be effective and avoid oto- or nephrotoxicity in adults (<a class="elsevierStyleCrossRef" href="#bib6">6</a>,<a class="elsevierStyleCrossRef" href="#bib7">7</a>,<a class="elsevierStyleCrossRef" href="#bib8">8</a>). Because vancomycin activity is primarily time-dependent, the 24-h area under the curve (AUC0-24h) divided by the minimum inhibitor concentration (MIC) value (AUC0-24h/MIC) is a better predictor of efficacy. In adults with MIC values less than 1 μg/ml, trough concentrations greater than 10 µg/ml result in AUC0-24h/MIC values >400.In subsequent analyses addressing clinical pharmacology, it is important to note that vancomycin is water-soluble, has a limited plasma protein binding capacity (i.e., IgA and albumin) and is mainly eliminated renally by glomerular filtration, although its elimination is further modulated by renal tubular transport (<a class="elsevierStyleCrossRef" href="#bib4">4</a>). Compared with adults, neonates have a higher extracellular fluid volume and a limited renal elimination capacity (<a class="elsevierStyleCrossRef" href="#bib4">4</a>,<a class="elsevierStyleCrossRef" href="#bib9">9</a>). Consequently, vancomycin pharmacokinetics are different in neonates and undergo significant alterations as neonates mature. We aimed to provide a summary of published observations on vancomycin pharmacokinetics in neonates and a subsequent discussion on areas of further research.BIBLIOGRAPHIC SEARCHThe bibliographic search was performed electronically using PubMed and Embase. Searches were performed with the following keywords: “pharmacokinetics vancomycin neonate”; “continuous infusion vancomycin neonate”; “ECMO vancomycin neonate”; “indomethacin vancomycin neonate”; “ibuprofen vancomycin neonate”; “vancomycin penetration CSF neonate” and “vancomycin toxicity neonate” with the limit of “human”. All studies published in August 2011 or earlier were included in the analysis. The bibliography of each article was examined, and selected articles were read carefully. In addition, the book Neofax: a Manual of Drugs Used in the Neonatal Care, by Young and Mangum (<a class="elsevierStyleCrossRef" href="#bib8">8</a>), was consulted. The bibliographic search resulted in 60 original articles, 10 review articles, and two book chapters; the publication year range was from 1961 to 2011.RESULTSSeventy-two studies were considered in this review. <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a> summarizes vancomycin dose guidelines based on serum creatinine levels <a class="elsevierStyleCrossRef" href="#bib10">10</a>. <a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a> provides two neonatal vancomycin-dosing strategies that are based on either postmenstrual age or serum creatinine levels (<a class="elsevierStyleCrossRef" href="#bib11">11</a>). <a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a> provides dosage guidelines based on postmenstrual age and weight (<a class="elsevierStyleCrossRef" href="#bib12">12</a>). Finally, <a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a> summarizes demographic and pharmacokinetic parameters of vancomycin in neonates as reported in the literature (<a class="elsevierStyleCrossRefs" href="#bib12">12–27</a>).<elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia><elsevierMultimedia ident="tbl3"></elsevierMultimedia><elsevierMultimedia ident="tbl4"></elsevierMultimedia>Median estimates of vancomycin pharmacokinetics in neonatesCompared with pharmacokinetic estimates in adults, the median distribution volume is higher in neonates, and the highest estimates are in the most preterm neonates (<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>). In contrast, vancomycin clearance is significantly lower in neonates compared with adults after correcting for body surface area (<a class="elsevierStyleCrossRef" href="#bib27">27</a>). When expressed in ml/min/kg, the clearance estimates are lowest in the most preterm neonates (0.98 ml/min/kg) (<a class="elsevierStyleCrossRef" href="#bib15">15</a>). In addition, <a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a> illustrates that there is at least a 2- to 3-fold difference in vancomycin clearance within the neonatal age range, which in part reflects maturation and other renal functions that are related to co-morbidity characteristics in neonates (<a class="elsevierStyleCrossRefs" href="#bib12">12–27</a>).Covariates that reflect maturation: creatinine, age and/or weightVancomycin is almost exclusively cleared by renal glomerular filtration because renal tubular functions are still immature in neonates (<a class="elsevierStyleCrossRef" href="#bib4">4</a>,<a class="elsevierStyleCrossRef" href="#bib9">9</a>). Either postmenstrual age or weight is a covariate of vancomycin clearance, presumably because these covariates serve as indicators of glomerular filtration rate maturation (<a class="elsevierStyleCrossRef" href="#bib28">28</a>). Vancomycin clearance is positively affected by weight, gestational age, postnatal age and postmenstrual age and negatively affected by creatinine levels (<a class="elsevierStyleCrossRefs" href="#bib10">10–28</a>). However, these covariates are interrelated because postmenstrual age is the sum of gestational and postnatal ages, whereas the correlation between weight and age is self-evident. Finally, a progressive decline in creatinine levels is associated with an increase in age (<a class="elsevierStyleCrossRefs" href="#tbl1">Tables 1–4</a>).Covariates reflect comorbidity characteristicsThe level of creatinine does not only reflect maturational changes, but it may also in part reflect renal impairment. At present, the use of neonatal creatinine levels to predict renal function is controversial due to residual maternal creatinine and bio-analytical issues (see the discussion section). Other comorbidity characteristics that affect vancomycin clearance are related to renal impairment, which are either primarily caused by a drug-related reduction in renal clearance or a lower endogenous renal clearance capacity or secondarily caused by a disease-related decrease in renal function (<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>).As documented by Frattarelli et al., growth restriction affects vancomycin clearance capacity (<a class="elsevierStyleCrossRef" href="#bib17">17</a>) in neonates (<28 days old), but this reduction in vancomycin clearance is limited (16-20%) and related to the reduced renal elimination capacity of these neonates (<a class="elsevierStyleCrossRef" href="#bib19">19</a>,<a class="elsevierStyleCrossRef" href="#bib29">29</a>).The association between patent ductus arteriosus (PDA) and reduced vancomycin clearance is likely related to pharmacological treatment with either ibuprofen or indomethacin. Either indomethacin or ibuprofen is administered to induce PDA closure. Asbury et al. (26, <a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>) quantified the impact of indomethacin on vancomycin clearance. Basically, indomethacin administration for PDA closure reduced vancomycin clearance by 50% (<a class="elsevierStyleCrossRef" href="#bib26">26</a>). Allegaert (<a class="elsevierStyleCrossRef" href="#bib30">30</a>) aimed to quantify the impact of indomethacin or ibuprofen on neonatal vancomycin clearance. Allegaert et al. confirmed the effect of indomethacin on vancomycin clearance (-40%), whereas ibuprofen reduced clearance by 28%. Therefore, indomethacin has a much higher effect on vancomycin clearance compared with ibuprofen (<a class="elsevierStyleCrossRef" href="#bib30">30</a>,<a class="elsevierStyleCrossRef" href="#bib31">31</a>).Seay et al. (<a class="elsevierStyleCrossRef" href="#bib21">21</a>) reported on the population pharmacokinetics of vancomycin in 192 patients and documented that dopamine reduced vancomycin clearance (<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>). In contrast, when dopamine was evaluated as one of the covariates of vancomycin clearance in a data set of 214 preterm neonates, size, renal function and PMA, but neither dopamine nor respiratory support, were major contributors to clearance variability in premature neonates, which caused 18% of the variability to be unexplained (<a class="elsevierStyleCrossRef" href="#bib28">28</a>). Extra-corporeal membrane oxygenation (ECMO) provides cardiopulmonary support for patients with potentially reversible respiratory and cardiac failure. Vancomycin clearance is decreased and its distribution volume is increased in neonates on ECMO (<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>) (<a class="elsevierStyleCrossRef" href="#bib24">24</a>,<a class="elsevierStyleCrossRef" href="#bib25">25</a>). Finally, an interaction at the level of competitive binding or inhibition of renal tubular transport processes likely explains the increase in vancomycin clearance during amoxicillin-clavulanic acid co-administration in a cohort of 70 neonates (<a class="elsevierStyleCrossRef" href="#bib22">22</a>).Cerebrospinal fluid (CSF) pharmacokinetics of vancomycinLittle is known concerning the penetration of vancomycin in neonatal CSF. Reiter and Doron (<a class="elsevierStyleCrossRef" href="#bib32">32</a>) reported CSF concentrations in three vancomycin-treated neonates. The case 1 subject was a 1264-g male who was delivered at 28 weeks of gestation, the case 2 subject was a 670-g male who was delivered at 31 weeks of gestation, and the case 3 subject was a 1150-g female who was delivered at 26 weeks of gestation. These three case subjects were treated with vancomycin at a daily dose of 20 mg/kg for 14 days. The article by Reiter and Doron (<a class="elsevierStyleCrossRef" href="#bib32">32</a>) includes additional clinical details. In case 1, the vancomycin CSF concentration was 5.6 µg/ml at 17.25 h after infusion on day 8 of therapy, and the CSF penetration rate, which was measured by the CSF to serum vancomycin concentration ratio, was 32%. In case 2, the vancomycin CSF concentration was 2.2 µg/ml at 10.7 h after intravenous administration on day 2 of the vancomycin therapy, and the CSF penetration rate of vancomycin was 26%. Patient 3 had a vancomycin CSF concentration of 5.5 µg/ml at 23 h after infusion on day 9 of the vancomycin therapy, and the CSF penetration rate was 42%. Schaad et al. (<a class="elsevierStyleCrossRef" href="#bib27">27</a>) (<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>) administered 10-15 mg of vancomycin intravenously to three neonates whose gestational age and body weight were unreported. The vancomycin CSF concentration range was 1.2-4.8 µg/ml (mean = 3.1 µg/ml), and the CSF penetration rate of vancomycin ranged from 7-21% (mean = 14%). Finally, Pau et al. (<a class="elsevierStyleCrossRef" href="#bib33">33</a>) reported the cases of two newborns who had received vancomycin intravenously and intra-ventricularly. The case 1 subject was a 1,280-g male who was born at 29 weeks of gestation and suffered from several diseases. This patient received the following vancomycin treatments: 50 mg/kg/day intravenously and 5-10 mg intra-ventricularly. The duration of vancomycin therapy was 26 days, and the vancomycin CSF concentration range was 12.7-92.1 µg/ml. Patient 2 was a female who was born at 31 weeks of gestation with multiple congenital anomalies. This neonate received the following vancomycin treatments: 60 mg/kg/day intravenously and 4 mg/day intraventricularly for 30 days. The vancomycin CSF concentration range was 9.5-55.3 µg/ml.DISCUSSIONNeonatal morbidity and mortality due to late-onset sepsis caused by coagulase-negative staphylococci or methicillin-resistant staphylococci has resulted in an increased necessity for the effective and safe administration of vancomycin in neonates. In the 1950s, Staphylococcus strains developed resistance to treatment with penicillin. Vancomycin arose as the treatment of choice for staphylococcal infections (<a class="elsevierStyleCrossRef" href="#bib34">34</a>), and its use declined in the 1960s when methicillin was preferred because of its safer toxicity profile compared with vancomycin (<a class="elsevierStyleCrossRef" href="#bib35">35</a>). In 1978, the use of vancomycin resurfaced as Streptococcus species developed further resistance to cephalosporins and other penicillins (<a class="elsevierStyleCrossRef" href="#bib35">35</a>).At present, vancomycin is the current treatment of choice for many neonatal staphylococcal infections. There are, however, no reports yet on the association between indices (i.e., peak, trough, and AUC0-24h) of vancomycin exposure and either bactericidal effects or nephro- or ototoxicity in neonates. Consequently, the target AUC0-24h/MIC index (≥400) of vancomycin, which is documented in adults, is used (<a class="elsevierStyleCrossRefs" href="#bib36">36–39</a>). Therefore, similar to a trough concentration of 10 µg/ml of vancomycin, the AUC0-24h/MIC target should be considered for any dosage recommendation to minimize treatment failure in neonates. Lustar and Metsvaht (<a class="elsevierStyleCrossRef" href="#bib38">38</a>) suggested that for mid-moderate neonatal infections, the AUC0-24h/MIC ratio should be ≥400, and for severe infections in immunocompromised hosts, such as cases of ventilator-associated pneumonia sustained by Staphylococcus aureus, this ratio should be ≥850. Staphylococcus warneri (<a class="elsevierStyleCrossRef" href="#bib40">40</a>), which has reduced glycopeptide susceptibility (MIC>2 µg/ml), also requires a higher vancomycin exposure.Obviously, this target necessitates the integration of the most relevant vancomycin pharmacokinetic covariates in neonatal dosing strategies. Van den Anker (<a class="elsevierStyleCrossRef" href="#bib39">39</a>) stated that the most important dosing strategies in neonates are based on a combination of postmenstrual and postnatal ages, which considers the known changes in body composition and renal function with a higher dose for the treatment of neonatal meningitis. Such strategies have been suggested or evaluated by different groups.Dosing guideline performanceYoung and Mangum (<a class="elsevierStyleCrossRef" href="#bib8">8</a>) suggested a vancomycin dosage of 15 mg/kg every 12 h in meningitis patients and 10 mg/kg every 12 h for the treatment of bacteremia. When the postmenstrual age is ≤29 weeks, the vancomycin dose should be administered every 12 or 18 h according to the postnatal age (>14 days postnatal age or younger). When the postmenstrual age range is 30-44 weeks, vancomycin should be administered every 8 or 12 h according to the postnatal age. When the postmenstrual age is ≥45 weeks, vancomycin should be administered every 6 h. This dosing guideline aims for a trough concentration between 5-10 µg/ml. However, Badran et al. (<a class="elsevierStyleCrossRef" href="#bib41">41</a>) recently illustrated that 51% of the patients in their neonatal unit attained the desired therapeutic trough concentration, and the trough concentration was <5 µg/ml in 33% of the neonates when these guidelines were utilized.To further illustrate the difficulties of effective dosing guideline implementation, we refer to the work of de Hoog et al. (<a class="elsevierStyleCrossRef" href="#bib20">20</a>). This group aimed to determine the best therapeutic dose for the treatment of vancomycin-sensitive bacterial infections in 108 neonates. The median gestational and postnatal ages were 28.9 weeks and 14 days, respectively, and the median body weight was 1,045 g (<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>). The vancomycin dose was 15 mg/kg every 12 h. Clearance was 0.057±0.0018 l/h/kg (variability = 31%); the distribution volume was 0.43±0.013 l/kg (variability = 25%), and t½ was 6±0.27 h (variability = 34%). Using this dosage (i.e., 15 mg/kg every 12 h), 95.5% of the initial trough concentration measurements were in the desired therapeutic range. Vancomycin trough concentrations before the second dose were 8.2±2.2 µg/ml. Trough concentrations before the fifth dose were 12.3±4.1 µg/ml. Only one trough concentration measurement was below 5 µg/ml. The vancomycin trough concentration range before the fifth dose was 15.3-20.6 µg/ml. Vancomycin accumulates in serum; accordingly, after the fifth dose, the peak concentration range was 16.6-34.5 µg/ml (mean = 25.8±5.0 µg/ml). The vancomycin trough concentration range was 5-15 µg/ml, and peak concentrations were <40 µg/ml (<a class="elsevierStyleCrossRef" href="#bib39">39</a>) (<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>). The authors suggested that a vancomycin dosage of 3×10 mg/kg per day leads to a minimized high peak serum concentration and a trough serum concentration that is too low. However, this assertion was derived from a prospective validation study of 22 neonates in the same unit. However, these results are concomitant with the internal (same unit) prospective validation efforts of Seay et al. (n = 20) and Marques-Minana et al. (n = 41) (<a class="elsevierStyleCrossRef" href="#bib21">21</a>,<a class="elsevierStyleCrossRef" href="#bib22">22</a>).Intermittent vs. continuous vancomycin administrationBecause the AUC concept aims to maintain the vancomycin concentration above a given threshold, it has been suggested that vancomycin can be administered as a continuous infusion (<a class="elsevierStyleCrossRefs" href="#bib42">42–45</a>). Plan et al. (<a class="elsevierStyleCrossRef" href="#bib42">42</a>) administered vancomycin as a continuous infusion of 15-25 mg/kg/day or 20-30 mg/kg/day to 145 neonates. The body weight range of the neonates was 500-1,160 g, and their gestational age range was 26-29 weeks. Using the abovementioned dosage, bactericidal efficacy was maintained, and most subjects had serum vancomycin concentrations within the therapeutic range. Pawlotsky et al. (<a class="elsevierStyleCrossRef" href="#bib43">43</a>) administered vancomycin as a 24-h constant infusion to two neonatal groups. Group 1 (n = 24) had a postmenstrual age range of 27-41 weeks and received 10-30 mg/kg/day according to the postmenstrual age. Group 2 (n = 29) had a postmenstrual age range of 28-51.5 weeks and received a loading dose of 7 mg/kg, followed by a continuous infusion of 10-40 mg/kg/day according to the postmenstrual age. The mean vancomycin serum concentrations at steady state were 11.0±3.1 and 15.4±6.2 µg/ml in Groups 1 and 2, respectively. Both regimens were well tolerated. Oudin et al. (<a class="elsevierStyleCrossRef" href="#bib44">44</a>) confirmed the feasibility of this approach (i.e., a 7-mg/kg loading dose and constant infusion of 30 mg/kg/day) but suggested increasing the initial loading dose to 20 mg/kg, which resulted in an exposure similar to that observed by Pawlotsky et al. (<a class="elsevierStyleCrossRef" href="#bib43">43</a>).The use and limitations of therapeutic drug monitoringAll pharmacokinetic studies demonstrate variability, which is only in part explained by weight, age, or creatinine level. This variability explains the use of therapeutic drug monitoring (TDM) of trough concentrations to ensure effectiveness and avoid nephrotoxicity. In contrast, the quantification of peak concentrations provides no additional monitoring value (<a class="elsevierStyleCrossRef" href="#bib4">4</a>,<a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib39">39</a>). Vancomycin-induced nephrotoxicity and ototoxicity were previously more common than is currently observed. After eliminating impurities from the early preparations of vancomycin, the incidence of primary adverse effects, such as nephrotoxicity, ototoxicity and “red man syndrome”, was reduced (<a class="elsevierStyleCrossRef" href="#bib46">46</a>). The most important risk factors for developing nephrotoxicity are the following: trough concentrations >10 µg/ml, concomitant treatment with aminoglycosides and/or prolonged therapy (>21 days) (<a class="elsevierStyleCrossRef" href="#bib47">47</a>,<a class="elsevierStyleCrossRef" href="#bib48">48</a>). Other risk factors include high peak concentrations, high total dose, preexisting renal failure, and concurrent treatment with amphotericin and/or furosemide. However, the role of these factors in the neonatal population is not well-established (<a class="elsevierStyleCrossRef" href="#bib49">49</a>). Proper vancomycin TDM minimized both glomerular and tubular nephrotoxicity in two studies in children and neonates (<a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib39">39</a>,<a class="elsevierStyleCrossRef" href="#bib50">50</a>,<a class="elsevierStyleCrossRef" href="#bib51">51</a>). In most cases, nephrotoxicity is reversible, even after high doses (<a class="elsevierStyleCrossRef" href="#bib52">52</a>). In contrast, there is no proven association between TDM and ototoxicity prevention (<a class="elsevierStyleCrossRef" href="#bib39">39</a>).Improving neonatal vancomycin effectiveness and toleranceDespite the number of reported pharmacokinetic studies on vancomycin in neonates, there are still relevant issues that require further consideration. First, covariates differ between the different studies, and the prospective validation of dosing guidelines is limited but urgently required to improve the predictability and extrapolation of dosing guidelines. This may be partially related to analytical issues specific to quantifying vancomycin or creatinine concentrations. Immunoassays that are routinely used to quantify vancomycin may overestimate vancomycin concentrations because of the cross-reactivity with some of the vancomycin degradation products or endogenous compounds, such as bilirubin (<a class="elsevierStyleCrossRef" href="#bib53">53</a>). The introduction of a more precise analytical method, such as liquid chromatography-tandem mass spectroscopy, should be considered. Creatinine levels initially increase and are most pronounced in the most immature neonates (<a class="elsevierStyleCrossRef" href="#bib54">54</a>). Postnatal observations also depend on techniques used to quantify creatinine levels (i.e., Jaffe colorimetry, compensated Jaffe quantification or enzymatic quantification). It is generally accepted that the Jaffe quantification method overestimates creatinine concentrations because of bilirubin and cephalosporin interference. This observation also indicates that the age- or weight-dependent creatinemia reference values will differ based on the quantification method used (<a class="elsevierStyleCrossRef" href="#bib55">55</a>). Until recently, none of the studies in the literature explicitly discussed creatinine quantification methods.Second, the external prospective validation of vancomycin dosing guidelines is only a first step to improving the efficacy and safety/tolerance of vancomycin. The AUC0-24h/MIC ratio is derived from extrapolated data in adults and necessitates prospective validation in neonates that includes an analysis of the potential add-on value of continuous administration with or without a loading dose (<a class="elsevierStyleCrossRef" href="#bib39">39</a>). Finally, data in specific settings, such as ECMO or meningitis, are limited and warrant a focused approach (<a class="elsevierStyleCrossRef" href="#bib56">56</a>). Until these data emerge, there are no well-validated dosing guidelines that can be used routinely throughout the world. Therefore, we strongly recommend that neonatal units prospectively validate one of the dosing guidelines provided (<a class="elsevierStyleCrossRefs" href="#tbl1">Tables 1–4</a>). Local validation efforts also enable caregivers to consider the local MIC values of the isolated pathogens.In conclusion, neonatal vancomycin pharmacokinetic data were reviewed, which was followed by a critical analysis of the literature. Renal function drives vancomycin pharmacokinetics. Consequently, age or weight are the most relevant covariates of vancomycin clearance and should be considered first in neonatal vancomycin dosing guidelines and further adjusted by indicators of renal dysfunction (e.g., ECMO and ibuprofen/indomethacin). In addition to the prospective validation of vancomycin dosing guidelines that includes an analysis of its effectiveness and tolerance, studies should focus on the relevance and the methods applied for therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates, whereas specific settings (i.e., ECMO and ibuprofen/indomethacin) warrant focused studies.AUTHOR CONTRIBUTIONSPacifici GM performed the systematic review and is the principal and corresponding author of the paper. Allegaert K is the second reviewer and verified the results. Both authors wrote the paper and approved the final version." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1582838" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:2 [ "identificador" => "cesec20" "titulo" => "BIBLIOGRAPHIC SEARCH" ] 3 => array:3 [ "identificador" => "cesec30" "titulo" => "RESULTS" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec40" "titulo" => "Median estimates of vancomycin pharmacokinetics in neonates" ] 1 => array:2 [ "identificador" => "cesec50" "titulo" => "Covariates that reflect maturation: creatinine, age and/or weight" ] 2 => array:2 [ "identificador" => "cesec60" "titulo" => "Covariates reflect comorbidity characteristics" ] 3 => array:2 [ "identificador" => "cesec70" "titulo" => "Cerebrospinal fluid (CSF) pharmacokinetics of vancomycin" ] ] ] 4 => array:3 [ "identificador" => "cesec80" "titulo" => "DISCUSSION" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec90" "titulo" => "Dosing guideline performance" ] 1 => array:2 [ "identificador" => "cesec100" "titulo" => "Intermittent vs. continuous vancomycin administration" ] 2 => array:2 [ "identificador" => "cesec110" "titulo" => "The use and limitations of therapeutic drug monitoring" ] 3 => array:2 [ "identificador" => "cesec120" "titulo" => "Improving neonatal vancomycin effectiveness and tolerance" ] ] ] 5 => array:2 [ "identificador" => "cesec130" "titulo" => "AUTHOR CONTRIBUTIONS" ] 6 => array:2 [ "identificador" => "xack639563" "titulo" => "ACKNOWLEDGMENTS" ] 7 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-11-22" "fechaAceptado" => "2012-03-05" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1582838" "palabras" => array:5 [ 0 => "Pharmacokinetics" 1 => "Vancomycin" 2 => "Neonate" 3 => "Developmental pharmacology" 4 => "Covariates" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:1 [ "resumen" => "Neonatal sepsis is common and is a major cause of morbidity and mortality. Vancomycin is the preferred treatment of several neonatal staphylococcal infections. The aim of this study was to review published data on vancomycin pharmacokinetics in neonates and to provide a critical analysis of the literature. A bibliographic search was performed using PubMed and Embase, and articles with a publication date of August 2011 or earlier were included in the analysis. Vancomycin pharmacokinetic estimates, which are different in neonates compared with adults, also exhibit extensive inter-neonatal variability. In neonates, several vancomycin dosing schedules have been proposed, mainly based on age (i.e., postmenstrual and postnatal), body weight or serum creatinine level. Other covariates [e.g., extracorporeal membrane oxygenation (ECMO), indomethacin or ibuprofen, and growth restriction] of vancomycin pharmacokinetics have been reported in neonates. Finally, vancomycin penetrates cerebrospinal fluid (range = 7-42%). Renal function drives vancomycin pharmacokinetics. Because either age or weight is the most relevant covariate of renal maturation, these covariates should be considered first in neonatal vancomycin dosing guidelines and further adjusted by renal dysfunction indicators (e.g., ECMO and ibuprofen/indomethacin). In addition to the prospective validation of available dosing guidelines, future studies should focus on the relevance of therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates." ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "No potential conflict of interest was reported." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Serum creatinine concentration (μmol/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Vancomycin (mg/kg) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval (h) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">20-29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">30-39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">40-49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">50-59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">60-79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">80-100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">>100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Check trough level at 24 h \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Vancomycin dosage guidelines developed by Grimsley and Thomson <a class="elsevierStyleCrossRef" href="#bib10">10</a>." ] ] 1 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Postmenstrual age (PMA)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Serum creatinine concentration (Scr)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PMA (weeks) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dose (mg/kg) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval (h) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Scr (mg/dl) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dose (mg/kg) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval (h) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">≤29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">≥1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">30-33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.3-1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">34-37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.0-1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">38-44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.7-0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">≥45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">≤0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Two neonatal vancomycin dosing strategies (postnatal age <60 days) developed by Capparelli et al. <a class="elsevierStyleCrossRef" href="#bib11">11</a>." ] ] 2 => array:7 [ "identificador" => "tbl3" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PMA (weeks) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Weight (g) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dose (mg/kg) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval (h) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top"><800 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">27-30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">800-1200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">31-36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1200-2000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">≥37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">>2000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Initial vancomycin dosage guidelines in neonates based on postmenstrual age (PMA) or weight, developed by McDougal et al. <a class="elsevierStyleCrossRef" href="#bib12">12</a>." ] ] 3 => array:7 [ "identificador" => "tbl4" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "GA = gestational age; PNA = postnatal age; n = number of cases; SGA = small for gestational age; AGA = appropriate for gestational age; ECMO = extracorporeal membrane oxygenation; PDA = patent ductus arteriosus; n.a. = not available." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comments \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">GAweeks \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">PNAdays \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Weightg \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dosemg/kg \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Clml/min/kg \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Vdl/kg \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">t½ h \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Peakµg/ml \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Troughµg/ml \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">First dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">28.4SD 2.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20.5SD 10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1069SD 435 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12.6q24 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.22SD 0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.53SD 0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.0SD 2.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">31.2SD 12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">9.5SD 3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Steady state \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="center" valign="top">The values refer to the 26-case population</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">+11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12.6q24 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.16SD 0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.52SD 0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.6SD 2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">46.4SD 15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">19.4SD 9.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Group 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">26.6SD 1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18SD 8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">908SD 254 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16q24 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.1SD 0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.55SD 0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.6SD 0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">28.1SD 1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.0SD 0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Group 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">29.4SD 2.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">23SD 14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1194SD 412 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18q18 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.19SD 0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.56SD 0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.6SD 0.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">27.9SD 1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.9SD 0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Group 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">35.9SD 3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24SD 18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2405SD 956 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15q12 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.36SD 0.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.57SD 0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4.9SD 0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">26.1SD 1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.5SD 0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Preterm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">25.9SD 1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">21<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">769SD 151 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">14.2SD 3.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.8b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.63SD 0.025 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10 hb \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">32.6SD 9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.7SD 4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Group 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">29.5SD 1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15.3SD 5.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1232SD 263 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.98<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.85<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">11.3<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">23.6<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10.5<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1516 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Group 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">30.1SD 1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">26.0SD 14.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1289SD 265 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.89<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.56<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8.7<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2 0.6<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">9.9<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Preterm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">26.5SD 2.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">71<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">880SD 340 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.2b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.68SD 0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.66b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">SGA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">27.3SD 2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">48SD 38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1140SD 590 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.17<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.52SD 0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7.7SD 4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">31.5SD 8.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.8SD 4.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">AGA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">26.5SD 1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">38SD 47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1535SD 986 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.84<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.72SD 0.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8.0SD 6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">30.6SD 10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8.3SD 6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">GA 29 wks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">29.3SD 3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">29SD 20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1297SD 640 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.07SD 0.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.48SD 0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.6SD 1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">22.6SD 3.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7.6SD 2.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Populationkinetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">30SD 2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">>90%< 2 wks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1000SD 840 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">116 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2.6<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.52<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8.5<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Populationkinetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">28.9c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">14c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1045c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15q12 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.4SD 0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.43SD .013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.0SD0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">34.3SD 7.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8.2SD 2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Populationkinetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">29.5SD 5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16.5SD 19.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">14921053 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">192 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.5<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.76<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">13.4-33.7(range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Populationkinetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">32.2SD 5.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16.9SD 10.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1700SD 800 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15q8-24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.96<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.57<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.3<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7.5<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top"><20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Preterm and full-term \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">31.0SD 7.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">9.1SD 4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1620SD 550 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.74SD 0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.51SD 0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7.2SD 2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">28.0SD 5.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4.9SD 2.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">ECMO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">38.8SD 2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12.7SD 5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3100SD 600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10q8 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.65SD 0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.45SD 0.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8.3SD 2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">27SD 4.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">13.7SD 2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">39.7SD 1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7.7SD 2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3400SD 400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10q8 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.79SD 0.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.39SD 0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.5SD 2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">23.0SD 5.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">13.2SD 4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">ECMO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">39SD 1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.6SD 1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3300SD 430 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15-20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.78SD 0.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.1SD 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16.9SD 9.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">30<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5- 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">29.3SD 4.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">33.9SD 19.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1780SD 1080 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.22SD 0.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.52SD 0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.6SD 1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">27.8SD 0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7.5SD 1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">PDA(indo) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">26.0SD 1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">17.6SD 7.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">810SD 160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Note E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.61SD 0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.57SD 0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">11.9SD 3.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">27.9SD 0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8.5SD 0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Preterm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">32<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.3<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1530<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10q24 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15ml/min/1.73 m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.74<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">9.8<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16.8<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.7<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Preterm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">34<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4.7<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1570<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15q24 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">27ml/min/1.73 m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.71<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.9<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">25.2<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Term \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">40<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2.6<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3070<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15q24 h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">30ml/min/1.73 m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.69<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.7<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">29.8<a class="elsevierStyleCrossRef" href="#tfn2">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">n.a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tfn2" "etiqueta" => "a" "nota" => "Mean, SD is not available;b Extracted figure; cMedian. Note A: The vancomycin doses were 10, 15, or 20 mg/kg. Note B: The vancomycin dose range was 9.2-18 mg/kg. Note C: The loading dose was 15±0.2 mg/kg, and the maintenance dose was 14.8±4.3 mg/kg. Note D: The loading dose was 15±0.2 mg/kg, and the maintenance dose was 29.6±13.1 mg/kg. Note E: The loading dose was 15 mg/kg, and the maintenance dose was 14.8±4. mg/kg. Note F: The dose range was 12.1-13.8 mg/kg (12.6±0.9 mg/kg), and the dosing interval range was 13-40 h (22.0±7.5 h). Note G: The dosing was initiated at 7.5, 10, 12, or 15 mg/kg, and the interval range was from q8 h to q24 h." ] ] ] "descripcion" => array:1 [ "en" => "Neonatal demographic data and pharmacokinetic parameters of vancomycin therapy. The results are presented as the mean±standard deviation unless otherwise stated." ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:56 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neonatal immunology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ RL Schelonka \n \t\t\t\t\t\t\t\t """ 1 => """ AJ Infante \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0146-0005(98)80003-7" "Revista" => array:7 [ "tituloSerie" => "Semin Perinatol" "fecha" => "1998" "volumen" => "22" "numero" => "1" "paginaInicial" => "2" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9523395" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recent advances in prevention of sepsis in the premature neonates in NICU" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ P Manzoni \n \t\t\t\t\t\t\t\t """ 1 => """ S Rizzollo \n \t\t\t\t\t\t\t\t """ 2 => """ L Decmebrino \n \t\t\t\t\t\t\t\t """ 3 => """ G Ruffinazzi \n \t\t\t\t\t\t\t\t """ 4 => """ A Rossi Ricci \n \t\t\t\t\t\t\t\t """ 5 => """ E Gallo \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Early Human Dev" "fecha" => "2011" "volumen" => "87" "numero" => "suppl 1" "paginaInicial" => "S1" "paginaFinal" => "S3" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality in 2008: a systematic analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ RE Black \n \t\t\t\t\t\t\t\t """ 1 => """ S Cousens \n \t\t\t\t\t\t\t\t """ 2 => """ HL Johnson \n \t\t\t\t\t\t\t\t """ 3 => """ JE Lawn \n \t\t\t\t\t\t\t\t """ 4 => """ I Rudan \n \t\t\t\t\t\t\t\t """ 5 => """ DG Bassani \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)60549-1" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "375" "numero" => "9730" "paginaInicial" => "1969" "paginaFinal" => "1987" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20466419" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics and administration regimens in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ M de Hoog \n \t\t\t\t\t\t\t\t """ 1 => """ JW Mouton \n \t\t\t\t\t\t\t\t """ 2 => """ JN van den Anker \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2165/00003088-200443070-00001" "Revista" => array:8 [ "tituloSerie" => "Clin Pharmacokinet" "fecha" => "2004" "volumen" => "43" "numero" => "7" "paginaInicial" => "417" "paginaFinal" => "440" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15139793" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S2213177920300196" "estado" => "S300" "issn" => "22131779" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protein synthesis inhibitors and miscellaneous and antibacterial agents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ HF Chambers \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:6 [ "editores" => "LLBrunton, JS LazoLazo, KLParker" "titulo" => "In the Goodman and Gilman's the Pharmacological Basis of Therapeutics" "paginaInicial" => "1194" "paginaFinal" => "1197" "edicion" => "11th Edition" "serieFecha" => "2006" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective evaluation of a vancomycin dosage guideline for neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ MH Gabriel \n \t\t\t\t\t\t\t\t """ 1 => """ GC Kildoo 3rd \n \t\t\t\t\t\t\t\t """ 2 => """ JL Gennrich \n \t\t\t\t\t\t\t\t """ 3 => """ HD Modanlou \n \t\t\t\t\t\t\t\t """ 4 => """ SR Collins \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Clin Pharm" "fecha" => "1991" "volumen" => "10" "numero" => "2" "paginaInicial" => "129" "paginaFinal" => "132" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2009729" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetics of antibiotics in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ Y Sato \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1442-200x.1997.tb03569.x" "Revista" => array:7 [ "tituloSerie" => "Acta Paediatr Jpn" "fecha" => "1997" "volumen" => "39" "numero" => "1" "paginaInicial" => "124" "paginaFinal" => "131" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9124044" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antimicrobials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ TE Young \n \t\t\t\t\t\t\t\t """ 1 => """ B Mangum \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "titulo" => "Neofax: a manual of drugs used in neonatal care" "paginaInicial" => "96" "paginaFinal" => "97" "edicion" => "23rd edition" "serieFecha" => "2010" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Developmental pharmacology: neonates are not just small adults" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ K Allegaert \n \t\t\t\t\t\t\t\t """ 1 => """ R Verbesselt \n \t\t\t\t\t\t\t\t """ 2 => """ G Naulaers \n \t\t\t\t\t\t\t\t """ 3 => """ JN van den Anker \n \t\t\t\t\t\t\t\t """ 4 => """ M Rayyan \n \t\t\t\t\t\t\t\t """ 5 => """ A Debeer \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1179/acb.2008.003" "Revista" => array:8 [ "tituloSerie" => "Acta Clin Belg" "fecha" => "2008" "volumen" => "63" "numero" => "1" "paginaInicial" => "16" "paginaFinal" => "24" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18386761" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0002934319306850" "estado" => "S300" "issn" => "00029343" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetics and dose requirements of vancomycin in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ C Grimsley \n \t\t\t\t\t\t\t\t """ 1 => """ AH Thomson \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/fn.81.3.f221" "Revista" => array:7 [ "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed" "fecha" => "1999" "volumen" => "81" "numero" => "3" "paginaInicial" => "F221" "paginaFinal" => "F227" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10525029" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The influences of renal function and maturation on vancomycin elimination in newborns and infants" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ EV Capparelli \n \t\t\t\t\t\t\t\t """ 1 => """ JR Lane \n \t\t\t\t\t\t\t\t """ 2 => """ GL Romanowski \n \t\t\t\t\t\t\t\t """ 3 => """ EJ McFeely \n \t\t\t\t\t\t\t\t """ 4 => """ W Murray \n \t\t\t\t\t\t\t\t """ 5 => """ P Sousa \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/00912700122010898" "Revista" => array:7 [ "tituloSerie" => "J Clin Pharmacol" "fecha" => "2001" "volumen" => "41" "numero" => "9" "paginaInicial" => "927" "paginaFinal" => "934" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11549096" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics and dosing in premature neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ A McDougal \n \t\t\t\t\t\t\t\t """ 1 => """ EW Ling \n \t\t\t\t\t\t\t\t """ 2 => """ M Levine \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00007691-199508000-00001" "Revista" => array:7 [ "tituloSerie" => "Ther Drug Monit" "fecha" => "1995" "volumen" => "17" "numero" => "4" "paginaInicial" => "319" "paginaFinal" => "326" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7482683" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The clinical pharmacology of vancomycin in seriously ill preterm infants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ MD Reed \n \t\t\t\t\t\t\t\t """ 1 => """ RM Kliegman \n \t\t\t\t\t\t\t\t """ 2 => """ JS Weiner \n \t\t\t\t\t\t\t\t """ 3 => """ M Huang \n \t\t\t\t\t\t\t\t """ 4 => """ TS Yamashita \n \t\t\t\t\t\t\t\t """ 5 => """ JL Blumer \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1203/00006450-198709000-00024" "Revista" => array:7 [ "tituloSerie" => "Pediatr Res" "fecha" => "1987" "volumen" => "22" "numero" => "3" "paginaInicial" => "360" "paginaFinal" => "363" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3658557" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics in very low birth weight neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ MB Leonard \n \t\t\t\t\t\t\t\t """ 1 => """ G Koren \n \t\t\t\t\t\t\t\t """ 2 => """ DK Stevenson \n \t\t\t\t\t\t\t\t """ 3 => """ CG Prober \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "1989" "volumen" => "8" "numero" => "5" "paginaInicial" => "282" "paginaFinal" => "286" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2657617" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics in preterm infants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ JK Machado \n \t\t\t\t\t\t\t\t """ 1 => """ R Feferbaum \n \t\t\t\t\t\t\t\t """ 2 => """ CE Kobayashi \n \t\t\t\t\t\t\t\t """ 3 => """ C Sanches \n \t\t\t\t\t\t\t\t """ 4 => """ SR Santos \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/s1807-59322007000400006" "Revista" => array:7 [ "tituloSerie" => "Clinics" "fecha" => "2007" "volumen" => "62" "numero" => "4" "paginaInicial" => "405" "paginaFinal" => "410" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17823702" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics and dose recommendations for preterm infants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ A James \n \t\t\t\t\t\t\t\t """ 1 => """ G Koren \n \t\t\t\t\t\t\t\t """ 2 => """ J Milliken \n \t\t\t\t\t\t\t\t """ 3 => """ S Soldin \n \t\t\t\t\t\t\t\t """ 4 => """ C Prober \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.31.1.52" "Revista" => array:7 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "1987" "volumen" => "31" "numero" => "1" "paginaInicial" => "52" "paginaFinal" => "54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3566238" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin elimination in human infants with intrauterine growth retardation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ DA Frattarelli \n \t\t\t\t\t\t\t\t """ 1 => """ H Ergun \n \t\t\t\t\t\t\t\t """ 2 => """ M Lulic-Botica \n \t\t\t\t\t\t\t\t """ 3 => """ VT Lehr \n \t\t\t\t\t\t\t\t """ 4 => """ JV Aranda \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.inf.0000186283.95728.34" "Revista" => array:7 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2005" "volumen" => "24" "numero" => "11" "paginaInicial" => "979" "paginaFinal" => "983" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16282933" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ CW Kildoo \n \t\t\t\t\t\t\t\t """ 1 => """ LM Lin \n \t\t\t\t\t\t\t\t """ 2 => """ MH Gabriel \n \t\t\t\t\t\t\t\t """ 3 => """ HL Folli \n \t\t\t\t\t\t\t\t """ 4 => """ HD Modanlou \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Dev Pharmacol Ther" "fecha" => "1990" "volumen" => "14" "numero" => "2" "paginaInicial" => "77" "paginaFinal" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2630235" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ YL Lo \n \t\t\t\t\t\t\t\t """ 1 => """ JG van Hasselt \n \t\t\t\t\t\t\t\t """ 2 => """ SC Heng \n \t\t\t\t\t\t\t\t """ 3 => """ CT Lim \n \t\t\t\t\t\t\t\t """ 4 => """ TC Lee \n \t\t\t\t\t\t\t\t """ 5 => """ BG Charles \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.01370-09" "Revista" => array:7 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2010" "volumen" => "54" "numero" => "6" "paginaInicial" => "2626" "paginaFinal" => "2632" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20385872" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin population pharmacokinetics in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ M de Hoog \n \t\t\t\t\t\t\t\t """ 1 => """ JW Schoemaker RC, Mouton \n \t\t\t\t\t\t\t\t """ 2 => """ JN van den Anker \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1067/mcp.2000.105353" "Revista" => array:7 [ "tituloSerie" => "Clin Pharmacol Ther" "fecha" => "2000" "volumen" => "67" "numero" => "4" "paginaInicial" => "360" "paginaFinal" => "367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10801244" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population pharmacokinetics of vancomycin in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ RE Seay \n \t\t\t\t\t\t\t\t """ 1 => """ RC Brundage \n \t\t\t\t\t\t\t\t """ 2 => """ PD Jensen \n \t\t\t\t\t\t\t\t """ 3 => """ CG Schilling \n \t\t\t\t\t\t\t\t """ 4 => """ BE Edgren \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/clpt.1994.120" "Revista" => array:7 [ "tituloSerie" => "Clin Pharmacol Ther" "fecha" => "1994" "volumen" => "56" "numero" => "2" "paginaInicial" => "169" "paginaFinal" => "175" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8062493" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population pharmacokinetic analysis of vancomycin in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ MR Marqués-Miñana \n \t\t\t\t\t\t\t\t """ 1 => """ A Saadeddin \n \t\t\t\t\t\t\t\t """ 2 => """ JE Peris \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2125.2010.03736.x" "Revista" => array:7 [ "tituloSerie" => "A new proposal of initial dosage guideline. Br J Clin Pharmacol" "fecha" => "2010" "volumen" => "70" "numero" => "5" "paginaInicial" => "713" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21039765" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Individualized pharmacokinetic profiles to compute vancomycin dosage and dosing interval in preterm infants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ RV Jarrett \n \t\t\t\t\t\t\t\t """ 1 => """ GA Marinkovich \n \t\t\t\t\t\t\t\t """ 2 => """ EL Gayle \n \t\t\t\t\t\t\t\t """ 3 => """ JW Bass \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00006454-199302000-00010" "Revista" => array:7 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "1993" "volumen" => "12" "numero" => "2" "paginaInicial" => "156" "paginaFinal" => "157" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8426775" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ ML Buck \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Pharmacotherapy" "fecha" => "1998" "volumen" => "18" "numero" => "5" "paginaInicial" => "1082" "paginaFinal" => "1086" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9758319" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ RD Amaker \n \t\t\t\t\t\t\t\t """ 1 => """ JT DiPiro \n \t\t\t\t\t\t\t\t """ 2 => """ J Bhatia \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.40.5.1139" "Revista" => array:7 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "1996" "volumen" => "40" "numero" => "5" "paginaInicial" => "1139" "paginaFinal" => "1142" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8723454" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ WH Asbury \n \t\t\t\t\t\t\t\t """ 1 => """ EH Darsey \n \t\t\t\t\t\t\t\t """ 2 => """ WB Rose \n \t\t\t\t\t\t\t\t """ 3 => """ JE Murphy \n \t\t\t\t\t\t\t\t """ 4 => """ DE Buffington \n \t\t\t\t\t\t\t\t """ 5 => """ CC Capers \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/106002809302700417" "Revista" => array:8 [ "tituloSerie" => "Ann Pharmacother" "fecha" => "1993" "volumen" => "27" "numero" => "4" "paginaInicial" => "490" "paginaFinal" => "496" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8477127" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109703003115" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical pharmacology and efficacy of vancomycin in pediatric patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ UB Schaad \n \t\t\t\t\t\t\t\t """ 1 => """ GH McCracken Jr \n \t\t\t\t\t\t\t\t """ 2 => """ JD Nelson \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0022-3476(80)80347-7" "Revista" => array:7 [ "tituloSerie" => "J Pediatr" "fecha" => "1980" "volumen" => "96" "numero" => "1" "paginaInicial" => "119" "paginaFinal" => "126" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7350291" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ BJ Anderson \n \t\t\t\t\t\t\t\t """ 1 => """ K Allegaert \n \t\t\t\t\t\t\t\t """ 2 => """ JN Van den Anker \n \t\t\t\t\t\t\t\t """ 3 => """ V Cossey \n \t\t\t\t\t\t\t\t """ 4 => """ NH Holford \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2125.2006.02725.x" "Revista" => array:7 [ "tituloSerie" => "Br J Clin Pharmacol" "fecha" => "2006" "volumen" => "63" "numero" => "1" "paginaInicial" => "75" "paginaFinal" => "84" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16869817" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal drug clearance in preterm neonates: relation to prenatal growth" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ K Allegaert \n \t\t\t\t\t\t\t\t """ 1 => """ BJ Anderson \n \t\t\t\t\t\t\t\t """ 2 => """ JN van den Anker \n \t\t\t\t\t\t\t\t """ 3 => """ S Vanhaesebrouck \n \t\t\t\t\t\t\t\t """ 4 => """ F de Zegher \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/FTD.0b013e31806db3f5" "Revista" => array:8 [ "tituloSerie" => "Ther Drug Monit" "fecha" => "2007" "volumen" => "29" "numero" => "3" "paginaInicial" => "284" "paginaFinal" => "291" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17529884" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0033062015000328" "estado" => "S300" "issn" => "00330620" ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib30" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The kinetic profile of vancomycin in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ R Silva \n \t\t\t\t\t\t\t\t """ 1 => """ E Reis \n \t\t\t\t\t\t\t\t """ 2 => """ MA Bispo \n \t\t\t\t\t\t\t\t """ 3 => """ AM Almeida \n \t\t\t\t\t\t\t\t """ 4 => """ IM Costa \n \t\t\t\t\t\t\t\t """ 5 => """ F Falcão \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.2042-7158.1998.tb03342.x" "Revista" => array:8 [ "tituloSerie" => "J Pharm Pharmacol" "fecha" => "1998" "volumen" => "50" "numero" => "11" "paginaInicial" => "1255" "paginaFinal" => "1260" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9877311" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673605666305" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib31" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The impact of ibuprofen or indomethacin on renal drug clearance in neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ K Allegaert \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/14767050903180965" "Revista" => array:7 [ "tituloSerie" => "J Matern Fetal Neonatal Med" "fecha" => "2009" "volumen" => "22" "numero" => "Suppl 3" "paginaInicial" => "88" "paginaFinal" => "91" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19701859" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib32" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin cerebrospinal fluid concentrations after intravenous administration in premature infants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ PD Reiter \n \t\t\t\t\t\t\t\t """ 1 => """ MW Doron \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:8 [ "tituloSerie" => "J Perinatol" "fecha" => "1996" "volumen" => "16" "numero" => "5" "paginaInicial" => "331" "paginaFinal" => "335" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8915929" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1885585716302948" "estado" => "S300" "issn" => "18855857" ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib33" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intraventricular vancomycin: observations of tolerance and pharmacokinetics in two infants with ventricular shunt infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ AK Pau \n \t\t\t\t\t\t\t\t """ 1 => """ RA Smego Jr \n \t\t\t\t\t\t\t\t """ 2 => """ MA Fisher \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Pediatr Infect Dis" "fecha" => "1986" "volumen" => "5" "numero" => "1" "paginaInicial" => "93" "paginaFinal" => "96" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3945581" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib34" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin and gentamicin in neonates: hindsight, current controversies, and forethought" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ PM Dawson \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00005237-200209000-00006" "Revista" => array:8 [ "tituloSerie" => "J Perinat Neonatal Nurs" "fecha" => "2002" "volumen" => "16" "numero" => "2" "paginaInicial" => "54" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12233945" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0213911111000598" "estado" => "S300" "issn" => "02139111" ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib35" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rationing antibiotic use in neonatal units" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ D Isaacs \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/fn.82.1.f1" "Revista" => array:7 [ "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed" "fecha" => "2000" "volumen" => "82" "numero" => "1" "paginaInicial" => "F1" "paginaFinal" => "F2" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10634830" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib36" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ PA Moise-Broder \n \t\t\t\t\t\t\t\t """ 1 => """ A Forrest \n \t\t\t\t\t\t\t\t """ 2 => """ MC Birmingham \n \t\t\t\t\t\t\t\t """ 3 => """ JJ Schentag \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2165/00003088-200443130-00005" "Revista" => array:7 [ "tituloSerie" => "Clin Pharmacokinet" "fecha" => "2004" "volumen" => "43" "numero" => "13" "paginaInicial" => "925" "paginaFinal" => "942" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15509186" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib37" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ A Frymoyer \n \t\t\t\t\t\t\t\t """ 1 => """ AL Hersh \n \t\t\t\t\t\t\t\t """ 2 => """ LZ Benet \n \t\t\t\t\t\t\t\t """ 3 => """ BJ Guglielmo \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/INF.0b013e3181906e40" "Revista" => array:8 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2009" "volumen" => "28" "numero" => "5" "paginaInicial" => "398" "paginaFinal" => "402" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19295465" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S221317792030010X" "estado" => "S300" "issn" => "22131779" ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib38" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Understanding pharmacokinetics/pharmacodynamics in managing neonatal sepsis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ I Lutsar \n \t\t\t\t\t\t\t\t """ 1 => """ T Metsvaht \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/QCO.0b013e328337bb42" "Revista" => array:7 [ "tituloSerie" => "Curr Opin Infect Dis" "fecha" => "2010" "volumen" => "23" "numero" => "3" "paginaInicial" => "201" "paginaFinal" => "207" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20179595" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib39" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Getting the dose of vancomycin right in the neonate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ JN van den Anker \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5414/CPP49247" "Revista" => array:7 [ "tituloSerie" => "Int J Clin Pharmacol Ther" "fecha" => "2011" "volumen" => "49" "numero" => "4" "paginaInicial" => "247" "paginaFinal" => "249" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21429437" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib40" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased vancomycin susceptibility of coagulase-negative staphylococci in a neonatal intensive care unit: evidence of spread of Staphylococcus warneri" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ KJ Center \n \t\t\t\t\t\t\t\t """ 1 => """ AC Reboli \n \t\t\t\t\t\t\t\t """ 2 => """ R Hubler \n \t\t\t\t\t\t\t\t """ 3 => """ GL Rodgers \n \t\t\t\t\t\t\t\t """ 4 => """ SS Long \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.41.10.4660-4665.2003" "Revista" => array:7 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2003" "volumen" => "41" "numero" => "10" "paginaInicial" => "4660" "paginaFinal" => "4665" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14532199" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib41" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetics of vancomycin in neonates admitted to the neonatology unit at the Jordan University Hospital" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ EF Badran \n \t\t\t\t\t\t\t\t """ 1 => """ A Shamayleh \n \t\t\t\t\t\t\t\t """ 2 => """ YM Irshaid \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5414/CP201456" "Revista" => array:7 [ "tituloSerie" => "Int J Clin Pharmacol Ther" "fecha" => "2011" "volumen" => "49" "numero" => "4" "paginaInicial" => "252" "paginaFinal" => "257" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21429439" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib42" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous-infusion vancomycin therapy for preterm neonates with suspected or documented Gram-positive infections: a new dosage schedule" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ O Plan \n \t\t\t\t\t\t\t\t """ 1 => """ G Cambonie \n \t\t\t\t\t\t\t\t """ 2 => """ E Barbotte \n \t\t\t\t\t\t\t\t """ 3 => """ P Meyer \n \t\t\t\t\t\t\t\t """ 4 => """ C Devine \n \t\t\t\t\t\t\t\t """ 5 => """ C Milesi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/adc.2007.128280" "Revista" => array:7 [ "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed" "fecha" => "2008" "volumen" => "93" "numero" => "6" "paginaInicial" => "F418" "paginaFinal" => "F421" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18450803" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib43" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Constant rate infusion of vancomycin in premature neonates: a new dosage schedule" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ F Pawlotsky \n \t\t\t\t\t\t\t\t """ 1 => """ A Thomas \n \t\t\t\t\t\t\t\t """ 2 => """ MF Kergueris \n \t\t\t\t\t\t\t\t """ 3 => """ T Debillon \n \t\t\t\t\t\t\t\t """ 4 => """ JC Roze \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1365-2125.1998.00763.x" "Revista" => array:7 [ "tituloSerie" => "Br J Clin Pharmacol" "fecha" => "1998" "volumen" => "46" "numero" => "2" "paginaInicial" => "163" "paginaFinal" => "167" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9723826" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib44" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin prescription in neonates and young infants: towards a simplified dosage" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ C Oudin \n \t\t\t\t\t\t\t\t """ 1 => 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"Revista" => array:7 [ "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed" "fecha" => "2009" "volumen" => "94" "numero" => "3" "paginaInicial" => "F233" "paginaFinal" => "F234" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19383865" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib46" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antibiotics and antifungals in neonatal intensive care units: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ V Fanos \n \t\t\t\t\t\t\t\t """ 1 => """ L Cuzzolin \n \t\t\t\t\t\t\t\t """ 2 => """ A Atzei \n \t\t\t\t\t\t\t\t """ 3 => """ M Testa \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:8 [ "tituloSerie" => "J Chemother" "fecha" => "2007" "volumen" => "19" "numero" => "1" "paginaInicial" => "5" "paginaFinal" => "20" "link" => array:1 [ 0 => 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"Pharmacokinetics and administration regimens of vancomycin in neonates, infants and children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ KA Rodvold \n \t\t\t\t\t\t\t\t """ 1 => """ JA Everett \n \t\t\t\t\t\t\t\t """ 2 => """ RD Pryka \n \t\t\t\t\t\t\t\t """ 3 => """ DM Kraus \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2165/00003088-199733010-00004" "Revista" => array:7 [ "tituloSerie" => "Clin Pharmacokinet" "fecha" => "1997" "volumen" => "33" "numero" => "1" "paginaInicial" => "32" "paginaFinal" => "51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9250422" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib50" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lack of nephrotoxicity in pediatric patients receiving concurrent vancomycin and aminoglycoside therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ MC Nahata \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000238512" "Revista" => array:7 [ "tituloSerie" => "Chemotherapy" "fecha" => "1987" "volumen" => "33" "numero" => "4" "paginaInicial" => "302" "paginaFinal" => "304" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3608631" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib51" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vancomycin does not enhance amikacin-induced tubular nephrotoxicity in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ MP Goren \n \t\t\t\t\t\t\t\t """ 1 => """ DK Baker Jr \n \t\t\t\t\t\t\t\t """ 2 => """ JL Shenep \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => 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What is the evidence for dose dependency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ SB Duffull \n \t\t\t\t\t\t\t\t """ 1 => """ EJ Begg \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Adverse Drug React Toxicol Rev" "fecha" => "1994" "volumen" => "13" "numero" => "2" "paginaInicial" => "103" "paginaFinal" => "114" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7918897" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib53" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors influencing the overestimation of plasma vancomycin concentrations measured by the Abbott TDx technique" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ T Iwamoto \n \t\t\t\t\t\t\t\t """ 1 => """ Y Kagawa \n \t\t\t\t\t\t\t\t """ 2 => """ M Kojima \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00007691-200502000-00012" "Revista" => array:7 [ "tituloSerie" => "Ther Drug Monit" "fecha" => "2005" "volumen" => "27" "numero" => "1" "paginaInicial" => "58" "paginaFinal" => "62" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15665748" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib54" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Postnatal trends in creatinemia and its covariates in extremely low birth weight (ELBW) neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ I George \n \t\t\t\t\t\t\t\t """ 1 => """ D Mekahli \n \t\t\t\t\t\t\t\t """ 2 => """ M Rayyan \n \t\t\t\t\t\t\t\t """ 3 => """ E Levtchenko \n \t\t\t\t\t\t\t\t """ 4 => """ K Allegaert \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00467-011-1883-0" "Revista" => array:7 [ "tituloSerie" => "Pediatr Nephrol" "fecha" => "2011" "volumen" => "26" "numero" => "10" "paginaInicial" => "1843" "paginaFinal" => "1849" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21499946" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib55" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Creatinaemia at birth is equal to maternal creatinaemia at delivery: does this paradigm still hold" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ M Kuppens \n \t\t\t\t\t\t\t\t """ 1 => """ I George \n \t\t\t\t\t\t\t\t """ 2 => """ L Lewi \n \t\t\t\t\t\t\t\t """ 3 => """ E Levtchenko \n \t\t\t\t\t\t\t\t """ 4 => """ K Allegaert \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "J Matern Fetal Neonatal Med" "fecha" => "2011; Aug 25" ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib56" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ H Mulla \n \t\t\t\t\t\t\t\t """ 1 => """ S Pooboni \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2125.2005.02432.x" "Revista" => array:7 [ "tituloSerie" => "Br J Clin Pharmacol" "fecha" => "2005" "volumen" => "60" "numero" => "3" "paginaInicial" => "265" "paginaFinal" => "275" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16120065" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack639563" "titulo" => "ACKNOWLEDGMENTS" "texto" => "This work was supported by the Ministry of the University and Scientific and Technologic Research (Rome, Italy). Karel Allegaert is supported by the Fund for Scientific Research, Flanders (Belgium) (FWO Vlaanderen, Fundamental Clinical investigatorship 1800209N)." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/0000006700000007/v1_202212011706/S180759322201780X/v1_202212011706/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/0000006700000007/v1_202212011706/S180759322201780X/v1_202212011706/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S180759322201780X?idApp=UINPBA00004N"]

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Gian Maria PacificiI,

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Tel.: 39 050-2218721

, Karel AllegaertII

I University of Pisa, Medical School, Department of Neurosciences, Section of Pharmacology, Pisa/IT

II Neonatal Intensive Care Unit, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Neonates have a higher risk of nosocomial infections due to humoral&#44; cellular and myeloid cell functions combined with the use of invasive techniques &#40;e&#46;g&#46;&#44; central venous catheter and endotracheal intubation&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib1">1</a>&#41;&#46; Because neonatal bacterial sepsis has mortality rates of 10-20&#37; and causes morbidity in 25-30&#37; of survivors &#40;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#44;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#41;&#44; effective and tolerated anti-microbiologic treatment regimens are required&#46; Coagulase-negative <span class="elsevierStyleItalic">Staphylococci</span> and <span class="elsevierStyleItalic">Staphylococcus aureus</span> are common nosocomial bacterial pathogens&#44; and vancomycin is the first-choice antibiotic to treat these pathogens&#44; especially in methicillin-resistance settings &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#41;&#46; Vancomycin is active against gram-positive bacteria&#46; <span class="elsevierStyleItalic">Staphylococcus epidermis</span>&#44; including methicillin-resistant strains&#44; are inhibited by vancomycin concentrations of 1-4 &#181;g&#47;ml&#46; <span class="elsevierStyleItalic">Staphylococcus pyogenes</span>&#44; <span class="elsevierStyleItalic">Streptococcus pneumonia&#44;</span> and <span class="elsevierStyleItalic">Streptococcus viridans</span> are susceptible to 2 &#181;g&#47;ml vancomycin&#46; <span class="elsevierStyleItalic">Bacillus spp&#46;</span> are inhibited by 2 &#181;g&#47;ml&#44; <span class="elsevierStyleItalic">Corynebacterium spp</span>&#46; by 0&#46;04-3&#46;1 &#181;g&#47;ml and <span class="elsevierStyleItalic">Clostridium spp</span>&#46; by 0&#46;39-6 &#181;g&#47;ml vancomycin &#40;<a class="elsevierStyleCrossRef" href="#bib5">5</a>&#41;&#46; Peak and trough concentrations of vancomycin should be &#60;40 &#956;g&#47;ml and &#60;10 &#956;g&#47;ml&#44; respectively&#44; to both be effective and avoid oto- or nephrotoxicity in adults &#40;<a class="elsevierStyleCrossRef" href="#bib6">6</a>&#44;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#44;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#41;&#46; Because vancomycin activity is primarily time-dependent&#44; the 24-h area under the curve &#40;AUC<span class="elsevierStyleInf">0-24h</span>&#41; divided by the minimum inhibitor concentration &#40;MIC&#41; value &#40;AUC<span class="elsevierStyleInf">0-24h</span>&#47;MIC&#41; is a better predictor of efficacy&#46; In adults with MIC values less than 1 &#956;g&#47;ml&#44; trough concentrations greater than 10 &#181;g&#47;ml result in AUC<span class="elsevierStyleInf">0-24h</span>&#47;MIC values &#62;400&#46;</p><p id="para20" class="elsevierStylePara elsevierViewall">In subsequent analyses addressing clinical pharmacology&#44; it is important to note that vancomycin is water-soluble&#44; has a limited plasma protein binding capacity &#40;i&#46;e&#46;&#44; IgA and albumin&#41; and is mainly eliminated renally by glomerular filtration&#44; although its elimination is further modulated by renal tubular transport &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#41;&#46; Compared with adults&#44; neonates have a higher extracellular fluid volume and a limited renal elimination capacity &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#44;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#41;&#46; Consequently&#44; vancomycin pharmacokinetics are different in neonates and undergo significant alterations as neonates mature&#46; We aimed to provide a summary of published observations on vancomycin pharmacokinetics in neonates and a subsequent discussion on areas of further research&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">BIBLIOGRAPHIC SEARCH</span><p id="para30" class="elsevierStylePara elsevierViewall">The bibliographic search was performed electronically using PubMed and Embase&#46; Searches were performed with the following keywords&#58; &#8220;pharmacokinetics vancomycin neonate&#8221;&#59; &#8220;continuous infusion vancomycin neonate&#8221;&#59; &#8220;ECMO vancomycin neonate&#8221;&#59; &#8220;indomethacin vancomycin neonate&#8221;&#59; &#8220;ibuprofen vancomycin neonate&#8221;&#59; &#8220;vancomycin penetration CSF neonate&#8221; and &#8220;vancomycin toxicity neonate&#8221; with the limit of &#8220;human&#8221;&#46; All studies published in August 2011 or earlier were included in the analysis&#46; The bibliography of each article was examined&#44; and selected articles were read carefully&#46; In addition&#44; the book <span class="elsevierStyleItalic">Neofax&#58; a Manual of Drugs Used in the Neonatal Care</span>&#44; by Young and Mangum &#40;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#41;&#44; was consulted&#46; The bibliographic search resulted in 60 original articles&#44; 10 review articles&#44; and two book chapters&#59; the publication year range was from 1961 to 2011&#46;</p></span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">RESULTS</span><p id="para40" class="elsevierStylePara elsevierViewall">Seventy-two studies were considered in this review&#46; <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a> summarizes vancomycin dose guidelines based on serum creatinine levels <a class="elsevierStyleCrossRef" href="#bib10">10</a>&#46; <a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a> provides two neonatal vancomycin-dosing strategies that are based on either postmenstrual age or serum creatinine levels &#40;<a class="elsevierStyleCrossRef" href="#bib11">11</a>&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a> provides dosage guidelines based on postmenstrual age and weight &#40;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#41;&#46; Finally&#44; <a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a> summarizes demographic and pharmacokinetic parameters of vancomycin in neonates as reported in the literature &#40;<a class="elsevierStyleCrossRefs" href="#bib12">12&#8211;27</a>&#41;&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia><elsevierMultimedia ident="tbl3"></elsevierMultimedia><elsevierMultimedia ident="tbl4"></elsevierMultimedia><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle50">Median estimates of vancomycin pharmacokinetics in neonates</span><p id="para50" class="elsevierStylePara elsevierViewall">Compared with pharmacokinetic estimates in adults&#44; the median distribution volume is higher in neonates&#44; and the highest estimates are in the most preterm neonates &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41;&#46; In contrast&#44; vancomycin clearance is significantly lower in neonates compared with adults after correcting for body surface area &#40;<a class="elsevierStyleCrossRef" href="#bib27">27</a>&#41;&#46; When expressed in ml&#47;min&#47;kg&#44; the clearance estimates are lowest in the most preterm neonates &#40;0&#46;98 ml&#47;min&#47;kg&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#41;&#46; In addition&#44; <a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a> illustrates that there is at least a 2- to 3-fold difference in vancomycin clearance within the neonatal age range&#44; which in part reflects maturation and other renal functions that are related to co-morbidity characteristics in neonates &#40;<a class="elsevierStyleCrossRefs" href="#bib12">12&#8211;27</a>&#41;&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">Covariates that reflect maturation&#58; creatinine&#44; age and&#47;or weight</span><p id="para60" class="elsevierStylePara elsevierViewall">Vancomycin is almost exclusively cleared by renal glomerular filtration because renal tubular functions are still immature in neonates &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#44;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#41;&#46; Either postmenstrual age or weight is a covariate of vancomycin clearance&#44; presumably because these covariates serve as indicators of glomerular filtration rate maturation &#40;<a class="elsevierStyleCrossRef" href="#bib28">28</a>&#41;&#46; Vancomycin clearance is positively affected by weight&#44; gestational age&#44; postnatal age and postmenstrual age and negatively affected by creatinine levels &#40;<a class="elsevierStyleCrossRefs" href="#bib10">10&#8211;28</a>&#41;&#46; However&#44; these covariates are interrelated because postmenstrual age is the sum of gestational and postnatal ages&#44; whereas the correlation between weight and age is self-evident&#46; Finally&#44; a progressive decline in creatinine levels is associated with an increase in age &#40;<a class="elsevierStyleCrossRefs" href="#tbl1">Tables 1&#8211;4</a>&#41;&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">Covariates reflect comorbidity characteristics</span><p id="para70" class="elsevierStylePara elsevierViewall">The level of creatinine does not only reflect maturational changes&#44; but it may also in part reflect renal impairment&#46; At present&#44; the use of neonatal creatinine levels to predict renal function is controversial due to residual maternal creatinine and bio-analytical issues &#40;see the discussion section&#41;&#46; Other comorbidity characteristics that affect vancomycin clearance are related to renal impairment&#44; which are either primarily caused by a drug-related reduction in renal clearance or a lower endogenous renal clearance capacity or secondarily caused by a disease-related decrease in renal function &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41;&#46;</p><p id="para80" class="elsevierStylePara elsevierViewall">As documented by Frattarelli et al&#46;&#44; growth restriction affects vancomycin clearance capacity &#40;<a class="elsevierStyleCrossRef" href="#bib17">17</a>&#41; in neonates &#40;&#60;28 days old&#41;&#44; but this reduction in vancomycin clearance is limited &#40;16-20&#37;&#41; and related to the reduced renal elimination capacity of these neonates &#40;<a class="elsevierStyleCrossRef" href="#bib19">19</a>&#44;<a class="elsevierStyleCrossRef" href="#bib29">29</a>&#41;&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall">The association between patent ductus arteriosus &#40;PDA&#41; and reduced vancomycin clearance is likely related to pharmacological treatment with either ibuprofen or indomethacin&#46; Either indomethacin or ibuprofen is administered to induce PDA closure&#46; Asbury et al&#46; &#40;26&#44; <a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41; quantified the impact of indomethacin on vancomycin clearance&#46; Basically&#44; indomethacin administration for PDA closure reduced vancomycin clearance by 50&#37; &#40;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#41;&#46; Allegaert &#40;<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#41; aimed to quantify the impact of indomethacin or ibuprofen on neonatal vancomycin clearance&#46; Allegaert et al&#46; confirmed the effect of indomethacin on vancomycin clearance &#40;-40&#37;&#41;&#44; whereas ibuprofen reduced clearance by 28&#37;&#46; Therefore&#44; indomethacin has a much higher effect on vancomycin clearance compared with ibuprofen &#40;<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#44;<a class="elsevierStyleCrossRef" href="#bib31">31</a>&#41;&#46;</p><p id="para100" class="elsevierStylePara elsevierViewall">Seay et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib21">21</a>&#41; reported on the population pharmacokinetics of vancomycin in 192 patients and documented that dopamine reduced vancomycin clearance &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41;&#46; In contrast&#44; when dopamine was evaluated as one of the covariates of vancomycin clearance in a data set of 214 preterm neonates&#44; size&#44; renal function and PMA&#44; but neither dopamine nor respiratory support&#44; were major contributors to clearance variability in premature neonates&#44; which caused 18&#37; of the variability to be unexplained &#40;<a class="elsevierStyleCrossRef" href="#bib28">28</a>&#41;&#46; Extra-corporeal membrane oxygenation &#40;ECMO&#41; provides cardiopulmonary support for patients with potentially reversible respiratory and cardiac failure&#46; Vancomycin clearance is decreased and its distribution volume is increased in neonates on ECMO &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib24">24</a>&#44;<a class="elsevierStyleCrossRef" href="#bib25">25</a>&#41;&#46; Finally&#44; an interaction at the level of competitive binding or inhibition of renal tubular transport processes likely explains the increase in vancomycin clearance during amoxicillin-clavulanic acid co-administration in a cohort of 70 neonates &#40;<a class="elsevierStyleCrossRef" href="#bib22">22</a>&#41;&#46;</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Cerebrospinal fluid &#40;CSF&#41; pharmacokinetics of vancomycin</span><p id="para110" class="elsevierStylePara elsevierViewall">Little is known concerning the penetration of vancomycin in neonatal CSF&#46; Reiter and Doron &#40;<a class="elsevierStyleCrossRef" href="#bib32">32</a>&#41; reported CSF concentrations in three vancomycin-treated neonates&#46; The case 1 subject was a 1264-g male who was delivered at 28 weeks of gestation&#44; the case 2 subject was a 670-g male who was delivered at 31 weeks of gestation&#44; and the case 3 subject was a 1150-g female who was delivered at 26 weeks of gestation&#46; These three case subjects were treated with vancomycin at a daily dose of 20 mg&#47;kg for 14 days&#46; The article by Reiter and Doron &#40;<a class="elsevierStyleCrossRef" href="#bib32">32</a>&#41; includes additional clinical details&#46; In case 1&#44; the vancomycin CSF concentration was 5&#46;6 &#181;g&#47;ml at 17&#46;25 h after infusion on day 8 of therapy&#44; and the CSF penetration rate&#44; which was measured by the CSF to serum vancomycin concentration ratio&#44; was 32&#37;&#46; In case 2&#44; the vancomycin CSF concentration was 2&#46;2 &#181;g&#47;ml at 10&#46;7 h after intravenous administration on day 2 of the vancomycin therapy&#44; and the CSF penetration rate of vancomycin was 26&#37;&#46; Patient 3 had a vancomycin CSF concentration of 5&#46;5 &#181;g&#47;ml at 23 h after infusion on day 9 of the vancomycin therapy&#44; and the CSF penetration rate was 42&#37;&#46; Schaad et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib27">27</a>&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41; administered 10-15 mg of vancomycin intravenously to three neonates whose gestational age and body weight were unreported&#46; The vancomycin CSF concentration range was 1&#46;2-4&#46;8 &#181;g&#47;ml &#40;mean &#61; 3&#46;1 &#181;g&#47;ml&#41;&#44; and the CSF penetration rate of vancomycin ranged from 7-21&#37; &#40;mean &#61; 14&#37;&#41;&#46; Finally&#44; Pau et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib33">33</a>&#41; reported the cases of two newborns who had received vancomycin intravenously and intra-ventricularly&#46; The case 1 subject was a 1&#44;280-g male who was born at 29 weeks of gestation and suffered from several diseases&#46; This patient received the following vancomycin treatments&#58; 50 mg&#47;kg&#47;day intravenously and 5-10 mg intra-ventricularly&#46; The duration of vancomycin therapy was 26 days&#44; and the vancomycin CSF concentration range was 12&#46;7-92&#46;1 &#181;g&#47;ml&#46; Patient 2 was a female who was born at 31 weeks of gestation with multiple congenital anomalies&#46; This neonate received the following vancomycin treatments&#58; 60 mg&#47;kg&#47;day intravenously and 4 mg&#47;day intraventricularly for 30 days&#46; The vancomycin CSF concentration range was 9&#46;5-55&#46;3 &#181;g&#47;ml&#46;</p></span></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">DISCUSSION</span><p id="para120" class="elsevierStylePara elsevierViewall">Neonatal morbidity and mortality due to late-onset sepsis caused by coagulase-negative <span class="elsevierStyleItalic">staphylococci</span> or methicillin-resistant <span class="elsevierStyleItalic">staphylococci</span> has resulted in an increased necessity for the effective and safe administration of vancomycin in neonates&#46; In the 1950s&#44; <span class="elsevierStyleItalic">Staphylococcus</span> strains developed resistance to treatment with penicillin&#46; Vancomycin arose as the treatment of choice for staphylococcal infections &#40;<a class="elsevierStyleCrossRef" href="#bib34">34</a>&#41;&#44; and its use declined in the 1960s when methicillin was preferred because of its safer toxicity profile compared with vancomycin &#40;<a class="elsevierStyleCrossRef" href="#bib35">35</a>&#41;&#46; In 1978&#44; the use of vancomycin resurfaced as <span class="elsevierStyleItalic">Streptococcus</span> species developed further resistance to cephalosporins and other penicillins &#40;<a class="elsevierStyleCrossRef" href="#bib35">35</a>&#41;&#46;</p><p id="para130" class="elsevierStylePara elsevierViewall">At present&#44; vancomycin is the current treatment of choice for many neonatal staphylococcal infections&#46; There are&#44; however&#44; no reports yet on the association between indices &#40;i&#46;e&#46;&#44; peak&#44; trough&#44; and AUC<span class="elsevierStyleInf">0-24h</span>&#41; of vancomycin exposure and either bactericidal effects or nephro- or ototoxicity in neonates&#46; Consequently&#44; the target AUC<span class="elsevierStyleInf">0-24h</span>&#47;MIC index &#40;&#8805;400&#41; of vancomycin&#44; which is documented in adults&#44; is used &#40;<a class="elsevierStyleCrossRefs" href="#bib36">36&#8211;39</a>&#41;&#46; Therefore&#44; similar to a trough concentration of 10 &#181;g&#47;ml of vancomycin&#44; the AUC<span class="elsevierStyleInf">0-24h</span>&#47;MIC target should be considered for any dosage recommendation to minimize treatment failure in neonates&#46; Lustar and Metsvaht &#40;<a class="elsevierStyleCrossRef" href="#bib38">38</a>&#41; suggested that for mid-moderate neonatal infections&#44; the AUC<span class="elsevierStyleInf">0-24h</span>&#47;MIC ratio should be &#8805;400&#44; and for severe infections in immunocompromised hosts&#44; such as cases of ventilator-associated pneumonia sustained by <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; this ratio should be &#8805;850&#46; <span class="elsevierStyleItalic">Staphylococcus warneri</span> &#40;<a class="elsevierStyleCrossRef" href="#bib40">40</a>&#41;&#44; which has reduced glycopeptide susceptibility &#40;MIC&#62;2 &#181;g&#47;ml&#41;&#44; also requires a higher vancomycin exposure&#46;</p><p id="para140" class="elsevierStylePara elsevierViewall">Obviously&#44; this target necessitates the integration of the most relevant vancomycin pharmacokinetic covariates in neonatal dosing strategies&#46; Van den Anker &#40;<a class="elsevierStyleCrossRef" href="#bib39">39</a>&#41; stated that the most important dosing strategies in neonates are based on a combination of postmenstrual and postnatal ages&#44; which considers the known changes in body composition and renal function with a higher dose for the treatment of neonatal meningitis&#46; Such strategies have been suggested or evaluated by different groups&#46;</p><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Dosing guideline performance</span><p id="para150" class="elsevierStylePara elsevierViewall">Young and Mangum &#40;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#41; suggested a vancomycin dosage of 15 mg&#47;kg every 12 h in meningitis patients and 10 mg&#47;kg every 12 h for the treatment of bacteremia&#46; When the postmenstrual age is &#8804;29 weeks&#44; the vancomycin dose should be administered every 12 or 18 h according to the postnatal age &#40;&#62;14 days postnatal age or younger&#41;&#46; When the postmenstrual age range is 30-44 weeks&#44; vancomycin should be administered every 8 or 12 h according to the postnatal age&#46; When the postmenstrual age is &#8805;45 weeks&#44; vancomycin should be administered every 6 h&#46; This dosing guideline aims for a trough concentration between 5-10 &#181;g&#47;ml&#46; However&#44; Badran et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib41">41</a>&#41; recently illustrated that 51&#37; of the patients in their neonatal unit attained the desired therapeutic trough concentration&#44; and the trough concentration was &#60;5 &#181;g&#47;ml in 33&#37; of the neonates when these guidelines were utilized&#46;</p><p id="para160" class="elsevierStylePara elsevierViewall">To further illustrate the difficulties of effective dosing guideline implementation&#44; we refer to the work of de Hoog et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib20">20</a>&#41;&#46; This group aimed to determine the best therapeutic dose for the treatment of vancomycin-sensitive bacterial infections in 108 neonates&#46; The median gestational and postnatal ages were 28&#46;9 weeks and 14 days&#44; respectively&#44; and the median body weight was 1&#44;045 g &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41;&#46; The vancomycin dose was 15 mg&#47;kg every 12 h&#46; Clearance was 0&#46;057&#177;0&#46;0018 l&#47;h&#47;kg &#40;variability &#61; 31&#37;&#41;&#59; the distribution volume was 0&#46;43&#177;0&#46;013 l&#47;kg &#40;variability &#61; 25&#37;&#41;&#44; and t<span class="elsevierStyleInf">&#189;</span> was 6&#177;0&#46;27 h &#40;variability &#61; 34&#37;&#41;&#46; Using this dosage &#40;i&#46;e&#46;&#44; 15 mg&#47;kg every 12 h&#41;&#44; 95&#46;5&#37; of the initial trough concentration measurements were in the desired therapeutic range&#46; Vancomycin trough concentrations before the second dose were 8&#46;2&#177;2&#46;2 &#181;g&#47;ml&#46; Trough concentrations before the fifth dose were 12&#46;3&#177;4&#46;1 &#181;g&#47;ml&#46; Only one trough concentration measurement was below 5 &#181;g&#47;ml&#46; The vancomycin trough concentration range before the fifth dose was 15&#46;3-20&#46;6 &#181;g&#47;ml&#46; Vancomycin accumulates in serum&#59; accordingly&#44; after the fifth dose&#44; the peak concentration range was 16&#46;6-34&#46;5 &#181;g&#47;ml &#40;mean &#61; 25&#46;8&#177;5&#46;0 &#181;g&#47;ml&#41;&#46; The vancomycin trough concentration range was 5-15 &#181;g&#47;ml&#44; and peak concentrations were &#60;40 &#181;g&#47;ml &#40;<a class="elsevierStyleCrossRef" href="#bib39">39</a>&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl4">Table 4</a>&#41;&#46; The authors suggested that a vancomycin dosage of 3&#215;10 mg&#47;kg per day leads to a minimized high peak serum concentration and a trough serum concentration that is too low&#46; However&#44; this assertion was derived from a prospective validation study of 22 neonates in the same unit&#46; However&#44; these results are concomitant with the internal &#40;same unit&#41; prospective validation efforts of Seay et al&#46; &#40;n &#61; 20&#41; and Marques-Minana et al&#46; &#40;n &#61; 41&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib21">21</a>&#44;<a class="elsevierStyleCrossRef" href="#bib22">22</a>&#41;&#46;</p></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Intermittent vs&#46; continuous vancomycin administration</span><p id="para170" class="elsevierStylePara elsevierViewall">Because the AUC concept aims to maintain the vancomycin concentration above a given threshold&#44; it has been suggested that vancomycin can be administered as a continuous infusion &#40;<a class="elsevierStyleCrossRefs" href="#bib42">42&#8211;45</a>&#41;&#46; Plan et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib42">42</a>&#41; administered vancomycin as a continuous infusion of 15-25 mg&#47;kg&#47;day or 20-30 mg&#47;kg&#47;day to 145 neonates&#46; The body weight range of the neonates was 500-1&#44;160 g&#44; and their gestational age range was 26-29 weeks&#46; Using the abovementioned dosage&#44; bactericidal efficacy was maintained&#44; and most subjects had serum vancomycin concentrations within the therapeutic range&#46; Pawlotsky et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib43">43</a>&#41; administered vancomycin as a 24-h constant infusion to two neonatal groups&#46; Group 1 &#40;n &#61; 24&#41; had a postmenstrual age range of 27-41 weeks and received 10-30 mg&#47;kg&#47;day according to the postmenstrual age&#46; Group 2 &#40;n &#61; 29&#41; had a postmenstrual age range of 28-51&#46;5 weeks and received a loading dose of 7 mg&#47;kg&#44; followed by a continuous infusion of 10-40 mg&#47;kg&#47;day according to the postmenstrual age&#46; The mean vancomycin serum concentrations at steady state were 11&#46;0&#177;3&#46;1 and 15&#46;4&#177;6&#46;2 &#181;g&#47;ml in Groups 1 and 2&#44; respectively&#46; Both regimens were well tolerated&#46; Oudin et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib44">44</a>&#41; confirmed the feasibility of this approach &#40;i&#46;e&#46;&#44; a 7-mg&#47;kg loading dose and constant infusion of 30 mg&#47;kg&#47;day&#41; but suggested increasing the initial loading dose to 20 mg&#47;kg&#44; which resulted in an exposure similar to that observed by Pawlotsky et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib43">43</a>&#41;&#46;</p></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">The use and limitations of therapeutic drug monitoring</span><p id="para180" class="elsevierStylePara elsevierViewall">All pharmacokinetic studies demonstrate variability&#44; which is only in part explained by weight&#44; age&#44; or creatinine level&#46; This variability explains the use of therapeutic drug monitoring &#40;TDM&#41; of trough concentrations to ensure effectiveness and avoid nephrotoxicity&#46; In contrast&#44; the quantification of peak concentrations provides no additional monitoring value &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#44;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib39">39</a>&#41;&#46; Vancomycin-induced nephrotoxicity and ototoxicity were previously more common than is currently observed&#46; After eliminating impurities from the early preparations of vancomycin&#44; the incidence of primary adverse effects&#44; such as nephrotoxicity&#44; ototoxicity and &#8220;red man syndrome&#8221;&#44; was reduced &#40;<a class="elsevierStyleCrossRef" href="#bib46">46</a>&#41;&#46; The most important risk factors for developing nephrotoxicity are the following&#58; trough concentrations &#62;10 &#181;g&#47;ml&#44; concomitant treatment with aminoglycosides and&#47;or prolonged therapy &#40;&#62;21 days&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib47">47</a>&#44;<a class="elsevierStyleCrossRef" href="#bib48">48</a>&#41;&#46; Other risk factors include high peak concentrations&#44; high total dose&#44; preexisting renal failure&#44; and concurrent treatment with amphotericin and&#47;or furosemide&#46; However&#44; the role of these factors in the neonatal population is not well-established &#40;<a class="elsevierStyleCrossRef" href="#bib49">49</a>&#41;&#46; Proper vancomycin TDM minimized both glomerular and tubular nephrotoxicity in two studies in children and neonates &#40;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib39">39</a>&#44;<a class="elsevierStyleCrossRef" href="#bib50">50</a>&#44;<a class="elsevierStyleCrossRef" href="#bib51">51</a>&#41;&#46; In most cases&#44; nephrotoxicity is reversible&#44; even after high doses &#40;<a class="elsevierStyleCrossRef" href="#bib52">52</a>&#41;&#46; In contrast&#44; there is no proven association between TDM and ototoxicity prevention &#40;<a class="elsevierStyleCrossRef" href="#bib39">39</a>&#41;&#46;</p></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Improving neonatal vancomycin effectiveness and tolerance</span><p id="para190" class="elsevierStylePara elsevierViewall">Despite the number of reported pharmacokinetic studies on vancomycin in neonates&#44; there are still relevant issues that require further consideration&#46; First&#44; covariates differ between the different studies&#44; and the prospective validation of dosing guidelines is limited but urgently required to improve the predictability and extrapolation of dosing guidelines&#46; This may be partially related to analytical issues specific to quantifying vancomycin or creatinine concentrations&#46; Immunoassays that are routinely used to quantify vancomycin may overestimate vancomycin concentrations because of the cross-reactivity with some of the vancomycin degradation products or endogenous compounds&#44; such as bilirubin &#40;<a class="elsevierStyleCrossRef" href="#bib53">53</a>&#41;&#46; The introduction of a more precise analytical method&#44; such as liquid chromatography-tandem mass spectroscopy&#44; should be considered&#46; Creatinine levels initially increase and are most pronounced in the most immature neonates &#40;<a class="elsevierStyleCrossRef" href="#bib54">54</a>&#41;&#46; Postnatal observations also depend on techniques used to quantify creatinine levels &#40;i&#46;e&#46;&#44; Jaffe colorimetry&#44; compensated Jaffe quantification or enzymatic quantification&#41;&#46; It is generally accepted that the Jaffe quantification method overestimates creatinine concentrations because of bilirubin and cephalosporin interference&#46; This observation also indicates that the age- or weight-dependent creatinemia reference values will differ based on the quantification method used &#40;<a class="elsevierStyleCrossRef" href="#bib55">55</a>&#41;&#46; Until recently&#44; none of the studies in the literature explicitly discussed creatinine quantification methods&#46;</p><p id="para200" class="elsevierStylePara elsevierViewall">Second&#44; the external prospective validation of vancomycin dosing guidelines is only a first step to improving the efficacy and safety&#47;tolerance of vancomycin&#46; The AUC<span class="elsevierStyleInf">0-24h</span>&#47;MIC ratio is derived from extrapolated data in adults and necessitates prospective validation in neonates that includes an analysis of the potential add-on value of continuous administration with or without a loading dose &#40;<a class="elsevierStyleCrossRef" href="#bib39">39</a>&#41;&#46; Finally&#44; data in specific settings&#44; such as ECMO or meningitis&#44; are limited and warrant a focused approach &#40;<a class="elsevierStyleCrossRef" href="#bib56">56</a>&#41;&#46; Until these data emerge&#44; there are no well-validated dosing guidelines that can be used routinely throughout the world&#46; Therefore&#44; we strongly recommend that neonatal units prospectively validate one of the dosing guidelines provided &#40;<a class="elsevierStyleCrossRefs" href="#tbl1">Tables 1&#8211;4</a>&#41;&#46; Local validation efforts also enable caregivers to consider the local MIC values of the isolated pathogens&#46;</p><p id="para210" class="elsevierStylePara elsevierViewall">In conclusion&#44; neonatal vancomycin pharmacokinetic data were reviewed&#44; which was followed by a critical analysis of the literature&#46; Renal function drives vancomycin pharmacokinetics&#46; Consequently&#44; age or weight are the most relevant covariates of vancomycin clearance and should be considered first in neonatal vancomycin dosing guidelines and further adjusted by indicators of renal dysfunction &#40;e&#46;g&#46;&#44; ECMO and ibuprofen&#47;indomethacin&#41;&#46; In addition to the prospective validation of vancomycin dosing guidelines that includes an analysis of its effectiveness and tolerance&#44; studies should focus on the relevance and the methods applied for therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates&#44; whereas specific settings &#40;i&#46;e&#46;&#44; ECMO and ibuprofen&#47;indomethacin&#41; warrant focused studies&#46;</p></span></span><span id="cesec130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">AUTHOR CONTRIBUTIONS</span><p id="para220" class="elsevierStylePara elsevierViewall">Pacifici GM performed the systematic review and is the principal and corresponding author of the paper&#46; Allegaert K is the second reviewer and verified the results&#46; Both authors wrote the paper and approved the final version&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:8 [
        0 => array:2 [
          "identificador" => "xpalclavsec1582838"
          "titulo" => "KEYWORDS"
        ]
        1 => array:2 [
          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
        ]
        2 => array:2 [
          "identificador" => "cesec20"
          "titulo" => "BIBLIOGRAPHIC SEARCH"
        ]
        3 => array:3 [
          "identificador" => "cesec30"
          "titulo" => "RESULTS"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "cesec40"
              "titulo" => "Median estimates of vancomycin pharmacokinetics in neonates"
            ]
            1 => array:2 [
              "identificador" => "cesec50"
              "titulo" => "Covariates that reflect maturation&#58; creatinine&#44; age and&#47;or weight"
            ]
            2 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Covariates reflect comorbidity characteristics"
            ]
            3 => array:2 [
              "identificador" => "cesec70"
              "titulo" => "Cerebrospinal fluid &#40;CSF&#41; pharmacokinetics of vancomycin"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "cesec80"
          "titulo" => "DISCUSSION"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "cesec90"
              "titulo" => "Dosing guideline performance"
            ]
            1 => array:2 [
              "identificador" => "cesec100"
              "titulo" => "Intermittent vs&#46; continuous vancomycin administration"
            ]
            2 => array:2 [
              "identificador" => "cesec110"
              "titulo" => "The use and limitations of therapeutic drug monitoring"
            ]
            3 => array:2 [
              "identificador" => "cesec120"
              "titulo" => "Improving neonatal vancomycin effectiveness and tolerance"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "cesec130"
          "titulo" => "AUTHOR CONTRIBUTIONS"
        ]
        6 => array:2 [
          "identificador" => "xack639563"
          "titulo" => "ACKNOWLEDGMENTS"
        ]
        7 => array:1 [
          "titulo" => "REFERENCES"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2011-11-22"
    "fechaAceptado" => "2012-03-05"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "KEYWORDS"
          "identificador" => "xpalclavsec1582838"
          "palabras" => array:5 [
            0 => "Pharmacokinetics"
            1 => "Vancomycin"
            2 => "Neonate"
            3 => "Developmental pharmacology"
            4 => "Covariates"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:1 [
        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Neonatal sepsis is common and is a major cause of morbidity and mortality&#46; Vancomycin is the preferred treatment of several neonatal staphylococcal infections&#46; The aim of this study was to review published data on vancomycin pharmacokinetics in neonates and to provide a critical analysis of the literature&#46; A bibliographic search was performed using PubMed and Embase&#44; and articles with a publication date of August 2011 or earlier were included in the analysis&#46; Vancomycin pharmacokinetic estimates&#44; which are different in neonates compared with adults&#44; also exhibit extensive inter-neonatal variability&#46; In neonates&#44; several vancomycin dosing schedules have been proposed&#44; mainly based on age &#40;i&#46;e&#46;&#44; postmenstrual and postnatal&#41;&#44; body weight or serum creatinine level&#46; Other covariates &#91;e&#46;g&#46;&#44; extracorporeal membrane oxygenation &#40;ECMO&#41;&#44; indomethacin or ibuprofen&#44; and growth restriction&#93; of vancomycin pharmacokinetics have been reported in neonates&#46; Finally&#44; vancomycin penetrates cerebrospinal fluid &#40;range &#61; 7-42&#37;&#41;&#46; Renal function drives vancomycin pharmacokinetics&#46; Because either age or weight is the most relevant covariate of renal maturation&#44; these covariates should be considered first in neonatal vancomycin dosing guidelines and further adjusted by renal dysfunction indicators &#40;e&#46;g&#46;&#44; ECMO and ibuprofen&#47;indomethacin&#41;&#46; In addition to the prospective validation of available dosing guidelines&#44; future studies should focus on the relevance of therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:1 [
        "nota" => "<p class="elsevierStyleNotepara" id="cenpara90">No potential conflict of interest was reported&#46;</p>"
      ]
    ]
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        "identificador" => "tbl1"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Serum creatinine concentration &#40;&#956;mol&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Vancomycin &#40;mg&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">20-29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">30-39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">40-49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">50-59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">60-79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">80-100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">&#62;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">Check trough level at 24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Vancomycin dosage guidelines developed by Grimsley and Thomson <a class="elsevierStyleCrossRef" href="#bib10">10</a>&#46;</p>"
        ]
      ]
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        "identificador" => "tbl2"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Postmenstrual age &#40;PMA&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Serum creatinine concentration &#40;Scr&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PMA &#40;weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dose &#40;mg&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Scr &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dose &#40;mg&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">&#8804;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#8805;1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">30-33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;3-1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">34-37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;0-1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">38-44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;7-0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">&#8805;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#8804;0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Two neonatal vancomycin dosing strategies &#40;postnatal age &#60;60 days&#41; developed by Capparelli et al&#46; <a class="elsevierStyleCrossRef" href="#bib11">11</a>&#46;</p>"
        ]
      ]
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        "identificador" => "tbl3"
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        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
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            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PMA &#40;weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dose &#40;mg&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Interval &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">&#60;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#60;800&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">27-30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">800-1200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">31-36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1200-2000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">&#8805;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#62;2000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Initial vancomycin dosage guidelines in neonates based on postmenstrual age &#40;PMA&#41; or weight&#44; developed by McDougal et al&#46; <a class="elsevierStyleCrossRef" href="#bib12">12</a>&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl4"
        "etiqueta" => "Table 4"
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        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">GA &#61; gestational age&#59; PNA &#61; postnatal age&#59; n &#61; number of cases&#59; SGA &#61; small for gestational age&#59; AGA &#61; appropriate for gestational age&#59; ECMO &#61; extracorporeal membrane oxygenation&#59; PDA &#61; patent ductus arteriosus&#59; n&#46;a&#46; &#61; not available&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">GAweeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">PNAdays&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Weightg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Dosemg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Clml&#47;min&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Vdl&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">t<span class="elsevierStyleInf">&#189;</span> h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Peak&#181;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Trough&#181;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">First dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">28&#46;4SD 2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&#46;5SD 10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1069SD 435&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&#46;6q24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;22SD 0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;53SD 0&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;0SD 2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">31&#46;2SD 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;5SD 3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">13</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Steady state&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="center" valign="top"><span class="elsevierStyleItalic">The values refer to the 26-case population</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#43;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&#46;6q24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;16SD 0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;52SD 0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;6SD 2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">46&#46;4SD 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">19&#46;4SD 9&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Group 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">26&#46;6SD 1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18SD 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">908SD 254&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16q24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;1SD 0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;55SD 0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;6SD 0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">28&#46;1SD 1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;0SD 0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">12</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Group 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29&#46;4SD 2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">23SD 14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1194SD 412&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18q18 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;19SD 0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;56SD 0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;6SD 0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">27&#46;9SD 1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;9SD 0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Group 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">35&#46;9SD 3&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">24SD 18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2405SD 956&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15q12 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;36SD 0&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;57SD 0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&#46;9SD 0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">26&#46;1SD 1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;5SD 0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Preterm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">25&#46;9SD 1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">21<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">769SD 151&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">14&#46;2SD 3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;8<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;63SD 0&#46;025&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10 h<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">32&#46;6SD 9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;7SD 4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">14</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Group 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29&#46;5SD 1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&#46;3SD 5&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1232SD 263&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note A</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;98<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;85<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">11&#46;3<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">23&#46;6<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&#46;5<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">15</span><span class="elsevierStyleItalic">16</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Group 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">30&#46;1SD 1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">26&#46;0SD 14&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1289SD 265&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note A</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;89<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;56<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;7<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 0&#46;6<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;9<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Preterm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">26&#46;5SD 2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">71<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">880SD 340&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note B</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;2<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;68SD 0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;66<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">SGA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">27&#46;3SD 2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">48SD 38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1140SD 590&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;17<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;52SD 0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;7SD 4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">31&#46;5SD 8&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;8SD 4&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">17</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">AGA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">26&#46;5SD 1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">38SD 47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1535SD 986&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;84<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;72SD 0&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;0SD 6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">30&#46;6SD 10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;3SD 6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">GA 29 wks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29&#46;3SD 3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29SD 20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1297SD 640&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note C</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;07SD 0&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;48SD 0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;6SD 1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">22&#46;6SD 3&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;6SD 2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">18</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Populationkinetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">30SD 2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#62;90&#37;&#60; 2 wks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1000SD 840&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#46;6<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;52<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;5<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">19</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Populationkinetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">28&#46;9<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">14<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1045<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">108&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15q12 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;4SD 0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;43SD &#46;013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;0SD0&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">34&#46;3SD 7&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;2SD 2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">20</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Populationkinetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29&#46;5SD 5&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16&#46;5SD 19&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">14921053&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">192&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note G</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;5<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;76<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13&#46;4-33&#46;7&#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">21</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Populationkinetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">32&#46;2SD 5&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16&#46;9SD 10&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1700SD 800&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15q8-24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;96<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;57<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;3<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;5<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#60;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">22</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Preterm and full-term&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">31&#46;0SD 7&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;1SD 4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1620SD 550&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note F</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;74SD 0&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;51SD 0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;2SD 2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">28&#46;0SD 5&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&#46;9SD 2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">23</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">ECMO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">38&#46;8SD 2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&#46;7SD 5&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3100SD 600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10q8 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;65SD 0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;45SD 0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;3SD 2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">27SD 4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13&#46;7SD 2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">24</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">39&#46;7SD 1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;7SD 2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3400SD 400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10q8 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;79SD 0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;39SD 0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;5SD 2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">23&#46;0SD 5&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13&#46;2SD 4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">ECMO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">39SD 1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;6SD 1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3300SD 430&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15-20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;78SD 0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;1SD 0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16&#46;9SD 9&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">30<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5- 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">25</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29&#46;3SD 4&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">33&#46;9SD 19&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1780SD 1080&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note D</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;22SD 0&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;52SD 0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;6SD 1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">27&#46;8SD 0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;5SD 1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">26</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">PDA&#40;indo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">26&#46;0SD 1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">17&#46;6SD 7&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">810SD 160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">Note E</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;61SD 0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;57SD 0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">11&#46;9SD 3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">27&#46;9SD 0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;5SD 0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Preterm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">32<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;3<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1530<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10q24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;74<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;8<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16&#46;8<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;7<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">27</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Preterm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">34<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&#46;7<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1570<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15q24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">27ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;71<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;9<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">25&#46;2<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Term&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">40<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#46;6<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3070<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15q24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">30ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;69<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;7<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29&#46;8<a class="elsevierStyleCrossRef" href="#tfn2">a</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">n&#46;a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tfn2"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">Mean&#44; SD is not available&#59;<span class="elsevierStyleSup">b</span> Extracted figure&#59; <span class="elsevierStyleSup">c</span>Median&#46;</p> <p class="elsevierStyleNotepara" id="cenpara20">Note A&#58; The vancomycin doses were 10&#44; 15&#44; or 20 mg&#47;kg&#46;</p> <p class="elsevierStyleNotepara" id="cenpara30">Note B&#58; The vancomycin dose range was 9&#46;2-18 mg&#47;kg&#46;</p> <p class="elsevierStyleNotepara" id="cenpara40">Note C&#58; The loading dose was 15&#177;0&#46;2 mg&#47;kg&#44; and the maintenance dose was 14&#46;8&#177;4&#46;3 mg&#47;kg&#46;</p> <p class="elsevierStyleNotepara" id="cenpara50">Note D&#58; The loading dose was 15&#177;0&#46;2 mg&#47;kg&#44; and the maintenance dose was 29&#46;6&#177;13&#46;1 mg&#47;kg&#46;</p> <p class="elsevierStyleNotepara" id="cenpara60">Note E&#58; The loading dose was 15 mg&#47;kg&#44; and the maintenance dose was 14&#46;8&#177;4&#46; mg&#47;kg&#46;</p> <p class="elsevierStyleNotepara" id="cenpara70">Note F&#58; The dose range was 12&#46;1-13&#46;8 mg&#47;kg &#40;12&#46;6&#177;0&#46;9 mg&#47;kg&#41;&#44; and the dosing interval range was 13-40 h &#40;22&#46;0&#177;7&#46;5 h&#41;&#46;</p> <p class="elsevierStyleNotepara" id="cenpara80">Note G&#58; The dosing was initiated at 7&#46;5&#44; 10&#44; 12&#44; or 15 mg&#47;kg&#44; and the interval range was from q8 h to q24 h&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Neonatal demographic data and pharmacokinetic parameters of vancomycin therapy&#46; The results are presented as the mean&#177;standard deviation unless otherwise stated&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:56 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal immunology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              RL Schelonka \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AJ Infante \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0146-0005(98)80003-7"
                      "Revista" => array:7 [
                        "tituloSerie" => "Semin Perinatol"
                        "fecha" => "1998"
                        "volumen" => "22"
                        "numero" => "1"
                        "paginaInicial" => "2"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9523395"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recent advances in prevention of sepsis in the premature neonates in NICU"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              P Manzoni \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Rizzollo \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              L Decmebrino \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              G Ruffinazzi \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              A Rossi Ricci \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              E Gallo \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Early Human Dev"
                        "fecha" => "2011"
                        "volumen" => "87"
                        "numero" => "suppl 1"
                        "paginaInicial" => "S1"
                        "paginaFinal" => "S3"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Child Health Epidemiology Reference Group of WHO and UNICEF&#46; Global&#44; regional&#44; and national causes of child mortality in 2008&#58; a systematic analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              RE Black \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Cousens \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              HL Johnson \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JE Lawn \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              I Rudan \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              DG Bassani \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(10)60549-1"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2010"
                        "volumen" => "375"
                        "numero" => "9730"
                        "paginaInicial" => "1969"
                        "paginaFinal" => "1987"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20466419"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics and administration regimens in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              M de Hoog \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JW Mouton \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JN van den Anker \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2165/00003088-200443070-00001"
                      "Revista" => array:8 [
                        "tituloSerie" => "Clin Pharmacokinet"
                        "fecha" => "2004"
                        "volumen" => "43"
                        "numero" => "7"
                        "paginaInicial" => "417"
                        "paginaFinal" => "440"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15139793"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S2213177920300196"
                          "estado" => "S300"
                          "issn" => "22131779"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protein synthesis inhibitors and miscellaneous and antibacterial agents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              HF Chambers \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:6 [
                        "editores" => "LLBrunton, JS LazoLazo, KLParker"
                        "titulo" => "In the Goodman and Gilman&#39;s the Pharmacological Basis of Therapeutics"
                        "paginaInicial" => "1194"
                        "paginaFinal" => "1197"
                        "edicion" => "11<span class="elsevierStyleSup">th</span> Edition"
                        "serieFecha" => "2006"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prospective evaluation of a vancomycin dosage guideline for neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              MH Gabriel \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              GC Kildoo 3rd \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JL Gennrich \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              HD Modanlou \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SR Collins \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Pharm"
                        "fecha" => "1991"
                        "volumen" => "10"
                        "numero" => "2"
                        "paginaInicial" => "129"
                        "paginaFinal" => "132"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2009729"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacokinetics of antibiotics in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              Y Sato \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1442-200x.1997.tb03569.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Acta Paediatr Jpn"
                        "fecha" => "1997"
                        "volumen" => "39"
                        "numero" => "1"
                        "paginaInicial" => "124"
                        "paginaFinal" => "131"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9124044"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antimicrobials"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              TE Young \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              B Mangum \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:5 [
                        "titulo" => "Neofax&#58; a manual of drugs used in neonatal care"
                        "paginaInicial" => "96"
                        "paginaFinal" => "97"
                        "edicion" => "23<span class="elsevierStyleSup">rd</span> edition"
                        "serieFecha" => "2010"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Developmental pharmacology&#58; neonates are not just small adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              K Allegaert \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              R Verbesselt \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              G Naulaers \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JN van den Anker \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              M Rayyan \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Debeer \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1179/acb.2008.003"
                      "Revista" => array:8 [
                        "tituloSerie" => "Acta Clin Belg"
                        "fecha" => "2008"
                        "volumen" => "63"
                        "numero" => "1"
                        "paginaInicial" => "16"
                        "paginaFinal" => "24"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18386761"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0002934319306850"
                          "estado" => "S300"
                          "issn" => "00029343"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacokinetics and dose requirements of vancomycin in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              C Grimsley \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AH Thomson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/fn.81.3.f221"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed"
                        "fecha" => "1999"
                        "volumen" => "81"
                        "numero" => "3"
                        "paginaInicial" => "F221"
                        "paginaFinal" => "F227"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10525029"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The influences of renal function and maturation on vancomycin elimination in newborns and infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              EV Capparelli \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JR Lane \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              GL Romanowski \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              EJ McFeely \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              W Murray \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              P Sousa \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/00912700122010898"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Pharmacol"
                        "fecha" => "2001"
                        "volumen" => "41"
                        "numero" => "9"
                        "paginaInicial" => "927"
                        "paginaFinal" => "934"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11549096"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics and dosing in premature neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              A McDougal \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              EW Ling \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Levine \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00007691-199508000-00001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ther Drug Monit"
                        "fecha" => "1995"
                        "volumen" => "17"
                        "numero" => "4"
                        "paginaInicial" => "319"
                        "paginaFinal" => "326"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7482683"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The clinical pharmacology of vancomycin in seriously ill preterm infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              MD Reed \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              RM Kliegman \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JS Weiner \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              M Huang \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              TS Yamashita \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              JL Blumer \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1203/00006450-198709000-00024"
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatr Res"
                        "fecha" => "1987"
                        "volumen" => "22"
                        "numero" => "3"
                        "paginaInicial" => "360"
                        "paginaFinal" => "363"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3658557"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics in very low birth weight neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              MB Leonard \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              G Koren \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              DK Stevenson \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              CG Prober \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1989"
                        "volumen" => "8"
                        "numero" => "5"
                        "paginaInicial" => "282"
                        "paginaFinal" => "286"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2657617"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics in preterm infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              JK Machado \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              R Feferbaum \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CE Kobayashi \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              C Sanches \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SR Santos \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1590/s1807-59322007000400006"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clinics"
                        "fecha" => "2007"
                        "volumen" => "62"
                        "numero" => "4"
                        "paginaInicial" => "405"
                        "paginaFinal" => "410"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17823702"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics and dose recommendations for preterm infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              A James \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              G Koren \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              J Milliken \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              S Soldin \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              C Prober \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.31.1.52"
                      "Revista" => array:7 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "1987"
                        "volumen" => "31"
                        "numero" => "1"
                        "paginaInicial" => "52"
                        "paginaFinal" => "54"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3566238"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin elimination in human infants with intrauterine growth retardation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              DA Frattarelli \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              H Ergun \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Lulic-Botica \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              VT Lehr \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JV Aranda \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.inf.0000186283.95728.34"
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "2005"
                        "volumen" => "24"
                        "numero" => "11"
                        "paginaInicial" => "979"
                        "paginaFinal" => "983"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16282933"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics in infants&#58; relationship to postconceptional age and serum creatinine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              CW Kildoo \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              LM Lin \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              MH Gabriel \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              HL Folli \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              HD Modanlou \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Dev Pharmacol Ther"
                        "fecha" => "1990"
                        "volumen" => "14"
                        "numero" => "2"
                        "paginaInicial" => "77"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2630235"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population pharmacokinetics of vancomycin in premature Malaysian neonates&#58; identification of predictors for dosing determination"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              YL Lo \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JG van Hasselt \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              SC Heng \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              CT Lim \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              TC Lee \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              BG Charles \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.01370-09"
                      "Revista" => array:7 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2010"
                        "volumen" => "54"
                        "numero" => "6"
                        "paginaInicial" => "2626"
                        "paginaFinal" => "2632"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20385872"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin population pharmacokinetics in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              M de Hoog \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JW Schoemaker RC&#44; Mouton \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JN van den Anker \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1067/mcp.2000.105353"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Pharmacol Ther"
                        "fecha" => "2000"
                        "volumen" => "67"
                        "numero" => "4"
                        "paginaInicial" => "360"
                        "paginaFinal" => "367"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10801244"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population pharmacokinetics of vancomycin in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              RE Seay \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              RC Brundage \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              PD Jensen \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              CG Schilling \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              BE Edgren \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/clpt.1994.120"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Pharmacol Ther"
                        "fecha" => "1994"
                        "volumen" => "56"
                        "numero" => "2"
                        "paginaInicial" => "169"
                        "paginaFinal" => "175"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8062493"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population pharmacokinetic analysis of vancomycin in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              MR Marqu&#233;s-Mi&#241;ana \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Saadeddin \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JE Peris \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2125.2010.03736.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "A new proposal of initial dosage guideline&#46; Br J Clin Pharmacol"
                        "fecha" => "2010"
                        "volumen" => "70"
                        "numero" => "5"
                        "paginaInicial" => "713"
                        "paginaFinal" => "720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21039765"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Individualized pharmacokinetic profiles to compute vancomycin dosage and dosing interval in preterm infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              RV Jarrett \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              GA Marinkovich \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              EL Gayle \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JW Bass \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00006454-199302000-00010"
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1993"
                        "volumen" => "12"
                        "numero" => "2"
                        "paginaInicial" => "156"
                        "paginaFinal" => "157"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8426775"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              ML Buck \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Pharmacotherapy"
                        "fecha" => "1998"
                        "volumen" => "18"
                        "numero" => "5"
                        "paginaInicial" => "1082"
                        "paginaFinal" => "1086"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9758319"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              RD Amaker \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JT DiPiro \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              J Bhatia \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.40.5.1139"
                      "Revista" => array:7 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "1996"
                        "volumen" => "40"
                        "numero" => "5"
                        "paginaInicial" => "1139"
                        "paginaFinal" => "1142"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8723454"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics in neonates and infants&#58; a retrospective evaluation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              WH Asbury \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              EH Darsey \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              WB Rose \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JE Murphy \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              DE Buffington \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              CC Capers \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/106002809302700417"
                      "Revista" => array:8 [
                        "tituloSerie" => "Ann Pharmacother"
                        "fecha" => "1993"
                        "volumen" => "27"
                        "numero" => "4"
                        "paginaInicial" => "490"
                        "paginaFinal" => "496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8477127"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109703003115"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical pharmacology and efficacy of vancomycin in pediatric patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              UB Schaad \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              GH McCracken Jr \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JD Nelson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0022-3476(80)80347-7"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "1980"
                        "volumen" => "96"
                        "numero" => "1"
                        "paginaInicial" => "119"
                        "paginaFinal" => "126"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7350291"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              BJ Anderson \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              K Allegaert \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JN Van den Anker \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              V Cossey \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              NH Holford \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2125.2006.02725.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Br J Clin Pharmacol"
                        "fecha" => "2006"
                        "volumen" => "63"
                        "numero" => "1"
                        "paginaInicial" => "75"
                        "paginaFinal" => "84"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16869817"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal drug clearance in preterm neonates&#58; relation to prenatal growth"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              K Allegaert \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              BJ Anderson \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JN van den Anker \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              S Vanhaesebrouck \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              F de Zegher \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/FTD.0b013e31806db3f5"
                      "Revista" => array:8 [
                        "tituloSerie" => "Ther Drug Monit"
                        "fecha" => "2007"
                        "volumen" => "29"
                        "numero" => "3"
                        "paginaInicial" => "284"
                        "paginaFinal" => "291"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17529884"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0033062015000328"
                          "estado" => "S300"
                          "issn" => "00330620"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The kinetic profile of vancomycin in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              R Silva \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              E Reis \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              MA Bispo \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              AM Almeida \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              IM Costa \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              F Falc&#227;o \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.2042-7158.1998.tb03342.x"
                      "Revista" => array:8 [
                        "tituloSerie" => "J Pharm Pharmacol"
                        "fecha" => "1998"
                        "volumen" => "50"
                        "numero" => "11"
                        "paginaInicial" => "1255"
                        "paginaFinal" => "1260"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9877311"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673605666305"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The impact of ibuprofen or indomethacin on renal drug clearance in neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              K Allegaert \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/14767050903180965"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Matern Fetal Neonatal Med"
                        "fecha" => "2009"
                        "volumen" => "22"
                        "numero" => "Suppl 3"
                        "paginaInicial" => "88"
                        "paginaFinal" => "91"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19701859"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin cerebrospinal fluid concentrations after intravenous administration in premature infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              PD Reiter \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              MW Doron \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:8 [
                        "tituloSerie" => "J Perinatol"
                        "fecha" => "1996"
                        "volumen" => "16"
                        "numero" => "5"
                        "paginaInicial" => "331"
                        "paginaFinal" => "335"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8915929"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1885585716302948"
                          "estado" => "S300"
                          "issn" => "18855857"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intraventricular vancomycin&#58; observations of tolerance and pharmacokinetics in two infants with ventricular shunt infections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              AK Pau \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              RA Smego Jr \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              MA Fisher \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatr Infect Dis"
                        "fecha" => "1986"
                        "volumen" => "5"
                        "numero" => "1"
                        "paginaInicial" => "93"
                        "paginaFinal" => "96"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3945581"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin and gentamicin in neonates&#58; hindsight&#44; current controversies&#44; and forethought"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              PM Dawson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00005237-200209000-00006"
                      "Revista" => array:8 [
                        "tituloSerie" => "J Perinat Neonatal Nurs"
                        "fecha" => "2002"
                        "volumen" => "16"
                        "numero" => "2"
                        "paginaInicial" => "54"
                        "paginaFinal" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12233945"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0213911111000598"
                          "estado" => "S300"
                          "issn" => "02139111"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rationing antibiotic use in neonatal units"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              D Isaacs \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/fn.82.1.f1"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed"
                        "fecha" => "2000"
                        "volumen" => "82"
                        "numero" => "1"
                        "paginaInicial" => "F1"
                        "paginaFinal" => "F2"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10634830"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              PA Moise-Broder \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Forrest \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              MC Birmingham \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JJ Schentag \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2165/00003088-200443130-00005"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Pharmacokinet"
                        "fecha" => "2004"
                        "volumen" => "43"
                        "numero" => "13"
                        "paginaInicial" => "925"
                        "paginaFinal" => "942"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15509186"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib37"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              A Frymoyer \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AL Hersh \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              LZ Benet \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              BJ Guglielmo \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/INF.0b013e3181906e40"
                      "Revista" => array:8 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "2009"
                        "volumen" => "28"
                        "numero" => "5"
                        "paginaInicial" => "398"
                        "paginaFinal" => "402"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19295465"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S221317792030010X"
                          "estado" => "S300"
                          "issn" => "22131779"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib38"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Understanding pharmacokinetics&#47;pharmacodynamics in managing neonatal sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              I Lutsar \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              T Metsvaht \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/QCO.0b013e328337bb42"
                      "Revista" => array:7 [
                        "tituloSerie" => "Curr Opin Infect Dis"
                        "fecha" => "2010"
                        "volumen" => "23"
                        "numero" => "3"
                        "paginaInicial" => "201"
                        "paginaFinal" => "207"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20179595"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib39"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Getting the dose of vancomycin right in the neonate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              JN van den Anker \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5414/CPP49247"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int J Clin Pharmacol Ther"
                        "fecha" => "2011"
                        "volumen" => "49"
                        "numero" => "4"
                        "paginaInicial" => "247"
                        "paginaFinal" => "249"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21429437"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib40"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decreased vancomycin susceptibility of coagulase-negative staphylococci in a neonatal intensive care unit&#58; evidence of spread of Staphylococcus warneri"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              KJ Center \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AC Reboli \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              R Hubler \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              GL Rodgers \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SS Long \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.41.10.4660-4665.2003"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2003"
                        "volumen" => "41"
                        "numero" => "10"
                        "paginaInicial" => "4660"
                        "paginaFinal" => "4665"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14532199"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib41"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacokinetics of vancomycin in neonates admitted to the neonatology unit at the Jordan University Hospital"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              EF Badran \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Shamayleh \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              YM Irshaid \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5414/CP201456"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int J Clin Pharmacol Ther"
                        "fecha" => "2011"
                        "volumen" => "49"
                        "numero" => "4"
                        "paginaInicial" => "252"
                        "paginaFinal" => "257"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21429439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib42"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Continuous-infusion vancomycin therapy for preterm neonates with suspected or documented Gram-positive infections&#58; a new dosage schedule"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              O Plan \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              G Cambonie \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              E Barbotte \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              P Meyer \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              C Devine \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              C Milesi \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/adc.2007.128280"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed"
                        "fecha" => "2008"
                        "volumen" => "93"
                        "numero" => "6"
                        "paginaInicial" => "F418"
                        "paginaFinal" => "F421"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18450803"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib43"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Constant rate infusion of vancomycin in premature neonates&#58; a new dosage schedule"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              F Pawlotsky \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Thomas \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              MF Kergueris \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              T Debillon \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JC Roze \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1365-2125.1998.00763.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Br J Clin Pharmacol"
                        "fecha" => "1998"
                        "volumen" => "46"
                        "numero" => "2"
                        "paginaInicial" => "163"
                        "paginaFinal" => "167"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9723826"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib44"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin prescription in neonates and young infants&#58; towards a simplified dosage"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              C Oudin \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              R Vialet \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Boulamery \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              C Martin \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              N Simon \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/adc.2010.196402"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed"
                        "fecha" => "2011"
                        "volumen" => "96"
                        "numero" => "5"
                        "paginaInicial" => "F365"
                        "paginaFinal" => "F370"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21378399"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib45"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Giving vancomycin as a continuous infusion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              ND Embleton \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Berrington \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/adc.2008.152322"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed"
                        "fecha" => "2009"
                        "volumen" => "94"
                        "numero" => "3"
                        "paginaInicial" => "F233"
                        "paginaFinal" => "F234"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19383865"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib46"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antibiotics and antifungals in neonatal intensive care units&#58; a review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              V Fanos \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              L Cuzzolin \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Atzei \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              M Testa \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:8 [
                        "tituloSerie" => "J Chemother"
                        "fecha" => "2007"
                        "volumen" => "19"
                        "numero" => "1"
                        "paginaInicial" => "5"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18618935"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0025775318305694"
                          "estado" => "S300"
                          "issn" => "00257753"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib47"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nephrotoxicity of vancomycin and aminoglycoside therapy separately and in combination"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              MB Goetz \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Sayers \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jac/32.2.325"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Antimicrob Chemother"
                        "fecha" => "1993"
                        "volumen" => "32"
                        "numero" => "2"
                        "paginaInicial" => "325"
                        "paginaFinal" => "334"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8226435"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib48"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nephrotoxicity of vancomycin&#44; alone and with an aminoglycoside"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              MJ Rybak \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              LM Albrecht \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              SC Boike \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              PH Chandrasekar \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jac/25.4.679"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Antimicrob Chemother"
                        "fecha" => "1990"
                        "volumen" => "25"
                        "numero" => "4"
                        "paginaInicial" => "679"
                        "paginaFinal" => "687"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2351627"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib49"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacokinetics and administration regimens of vancomycin in neonates&#44; infants and children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              KA Rodvold \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              JA Everett \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              RD Pryka \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              DM Kraus \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2165/00003088-199733010-00004"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Pharmacokinet"
                        "fecha" => "1997"
                        "volumen" => "33"
                        "numero" => "1"
                        "paginaInicial" => "32"
                        "paginaFinal" => "51"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9250422"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib50"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lack of nephrotoxicity in pediatric patients receiving concurrent vancomycin and aminoglycoside therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              MC Nahata \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000238512"
                      "Revista" => array:7 [
                        "tituloSerie" => "Chemotherapy"
                        "fecha" => "1987"
                        "volumen" => "33"
                        "numero" => "4"
                        "paginaInicial" => "302"
                        "paginaFinal" => "304"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3608631"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib51"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin does not enhance amikacin-induced tubular nephrotoxicity in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              MP Goren \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              DK Baker Jr \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JL Shenep \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1989"
                        "volumen" => "8"
                        "numero" => "5"
                        "paginaInicial" => "278"
                        "paginaFinal" => "282"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2657616"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib52"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vancomycin toxicity&#46; What is the evidence for dose dependency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              SB Duffull \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              EJ Begg \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Adverse Drug React Toxicol Rev"
                        "fecha" => "1994"
                        "volumen" => "13"
                        "numero" => "2"
                        "paginaInicial" => "103"
                        "paginaFinal" => "114"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7918897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib53"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors influencing the overestimation of plasma vancomycin concentrations measured by the Abbott TDx technique"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              T Iwamoto \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              Y Kagawa \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Kojima \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00007691-200502000-00012"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ther Drug Monit"
                        "fecha" => "2005"
                        "volumen" => "27"
                        "numero" => "1"
                        "paginaInicial" => "58"
                        "paginaFinal" => "62"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15665748"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib54"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Postnatal trends in creatinemia and its covariates in extremely low birth weight &#40;ELBW&#41; neonates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              I George \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              D Mekahli \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Rayyan \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              E Levtchenko \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              K Allegaert \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00467-011-1883-0"
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatr Nephrol"
                        "fecha" => "2011"
                        "volumen" => "26"
                        "numero" => "10"
                        "paginaInicial" => "1843"
                        "paginaFinal" => "1849"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21499946"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib55"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Creatinaemia at birth is equal to maternal creatinaemia at delivery&#58; does this paradigm still hold"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              M Kuppens \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              I George \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              L Lewi \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              E Levtchenko \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              K Allegaert \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "J Matern Fetal Neonatal Med"
                        "fecha" => "2011&#59; Aug 25"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib56"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              H Mulla \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              S Pooboni \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2125.2005.02432.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Br J Clin Pharmacol"
                        "fecha" => "2005"
                        "volumen" => "60"
                        "numero" => "3"
                        "paginaInicial" => "265"
                        "paginaFinal" => "275"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16120065"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
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        "titulo" => "ACKNOWLEDGMENTS"
        "texto" => "<p id="para230" class="elsevierStylePara elsevierViewall">This work was supported by the Ministry of the University and Scientific and Technologic Research &#40;Rome&#44; Italy&#41;&#46; Karel Allegaert is supported by the Fund for Scientific Research&#44; Flanders &#40;Belgium&#41; &#40;FWO Vlaanderen&#44; Fundamental Clinical investigatorship 1800209N&#41;&#46;</p>"
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Article information

ISSN: 18075932
Original language: English

DOI:10.6061/clinics/2012(07)21

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