Impact and quality of antimicrobial use in a referral pediatric intensive care unit | Enfermedades Infecciosas y Microbiología Clínica (English Edition)

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(a) Global antibacterial, antiviral, and antifungal drugs use; (b) six most used antibacterials during 2019." ] ] ] "textoCompleto" => "IntroductionAntimicrobial use (AU) is high in the pediatric population, especially among pediatric intensive care unit (PICU) patients.<a class="elsevierStyleCrossRefs" href="#bib0080">1,2</a> PICU patients are at risk of healthcare-associated infections, many of which are caused by resistant microorganisms that require broad-spectrum antibiotics.<a class="elsevierStyleCrossRef" href="#bib0085">2</a> PICUs also account for a high use of prophylactic antimicrobials.<a class="elsevierStyleCrossRefs" href="#bib0085">2,3</a> Antimicrobial stewardship programs (ASP) have proved their effectiveness in reducing AU in children,<a class="elsevierStyleCrossRefs" href="#bib0080">1,4,5</a> but data on the most effective interventions for children and, especially, for the critically ill pediatric population remain limited.<a class="elsevierStyleCrossRefs" href="#bib0080">1,4</a> Moreover, the use of classical AU measures in adults, such as “defined daily dose”, is discouraged in children because of the weight-based dosage of antimicrobials in this population.<a class="elsevierStyleCrossRefs" href="#bib0105">6,7</a>Data about the impact of PICU AU on the total hospital AU are lacking, although AU density could be up to three times higher than in ward units according to adult experience.<a class="elsevierStyleCrossRef" href="#bib0115">8</a> Also, very few studies have reported on ASP experiences in improving PICU quality of prescriptions (QP).<a class="elsevierStyleCrossRef" href="#bib0095">4</a>We aimed to describe AU and QP in a referral pediatric PICU and their impact on total hospital AU during the year 2019.MethodsSettingWe conducted a prospective observational study during 2019 in the 28-bed medical-surgical PICU of Hospital Sant Joan de Déu (Barcelona, Spain), a 268-pediatric-bed referral hospital with a full range of medical and surgical specialties and a 4-bed bone marrow transplant unit. The yearly number of hospital and PICU discharges are around 15,000 and 1200, respectively; among the latter, approximately 45% correspond to surgical patients (neurosurgery and cardiac surgery, one third each). A median of 6 extracorporeal membrane oxygenation procedures are performed yearly. The median Pediatric Risk of Mortality III score (PRISM III) for PICU-admitted patients in 2019 was 3.0 (IQR 2.8–3.6). The fully operational hospital ASP was implemented in January 2017. The main ASP strategy was face-to-face and/or electronic post-prescription review with feedback, together with other non-restrictive and educational strategies (see Suppl. Appendix 1).<a class="elsevierStyleCrossRef" href="#bib0100">5</a> This study was approved by the local ethics committee (ref. 32–20), which granted a waiver of individual informed consent. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.DesignData were collected from the e-prescription system and electronic clinical charts between January 1 and December 31, 2019. AU was calculated using days-of-therapy (DOT), defined as the aggregate sum of days that a specific antimicrobial was administered to a patient.<a class="elsevierStyleCrossRefs" href="#bib0100">5,9</a> To express density of AU, DOT was standardized to 100 days present (DP), considering one day present any amount of time in a calendar day spent by a patient in a definite hospital location.<a class="elsevierStyleCrossRef" href="#bib0100">5</a> Length-of-therapy (LOT) was used as a complementary AU indicator and defined as the duration of antimicrobial treatment in days. All systemic antibacterials, antifungals, and antivirals were included. Other complementary measures included length-of-stay (LOS), PICU readmission rates during the hospital admission (RR) and mortality rates within PICU admission (MR).QP was recorded based on monthly cross-sectional point-prevalence surveys (PPS) during which all the prescriptions for PICU patients were evaluated. For a prescription to be considered ‘optimal’ the prescribed drug should follow local reference guidelines accounting for patient allergies, and should be administered through the correct route, dose, and schedule, and for an appropriate duration (considering the actual duration or the expected duration recorded in the e-prescription system or in the patient medical record; Suppl. Appendix 1).<a class="elsevierStyleCrossRef" href="#bib0100">5</a>Statistical analysisCategorical variables were reported as proportions with 95% confidence intervals, and continuous variables as medians with interquartile ranges (IQRs). Correlation between variables was calculated using Pearson's correlation coefficient. Statistical analysis was carried out using SPSS version 25.0 software (IBM Corp., Armonk, NY, U.S.A.). Statistical significance was defined as a p-value<0.05.ResultsDuring 2019, 966 out of 1302 (74.2%) patients admitted in the PICU received antimicrobials. The PICU AU represented 13.5% of the global hospital AU during 2019 (PICU and all hospital areas absolute DOT: 6827 and 50,666, respectively). PICU presented a median density of AU 1.4 (IQR 1.3–1.5) times higher than that of the rest of hospital areas.Of the annual PICU AU, 88.5% corresponded to antibacterials, 5.8% to antivirals, and 5.7% to antifungals (see <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> and Suppl. Table 1). The parenteral route prevailed (82.1%). Year 2019 most frequently used antibiotics were cefazolin (183.6 DOT/100DP, 15.3%), amoxicillin-clavulanate (127.6 DOT/100DP, 10.6%), vancomycin (126.2 DOT/100DP, 10.5%), and cefotaxime (102.1 DOT/100DP, 8.5%). Acyclovir (30.8 DOT/100DP, 2.6%) and liposomal amphotericin B (21.2 DOT/100DP, 1.8%) were the most commonly used antiviral and antifungal drugs, respectively. Main results expressed in monthly medians are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Regarding QP, 168 antimicrobial prescriptions for 95 patients were evaluated in the 12 monthly PPS, 20.8% of which had a prophylactic intention (see Suppl. Table 2). High rates of optimal prescriptions were observed in all PPS (median 88.9%, IQR 81.8–90.9) except in August (57.1%) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The most frequent reasons for non-optimal prescription (19/168, 11.3%) were an inadequate spectrum (9/19, excessively broad and too narrow spectrum in 7 and 2, respectively) and excessive antimicrobial course duration (7/19). Nearly one third (30.0%) of non-optimal prescriptions had a prophylactic intention.In August 2019, due to an increase in critically ill patients with hematological malignancies, meropenem, piperacillin-tazobactam, and vancomycin use peaked, together with an increase in LOS and MR and a marked decrease in QP (see <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Other than this, LOT, LOS, RR, and MR remained stable during 2019 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). DOT and QP rates inversely correlated (Pearson's correlation; r=−0.565, p=0.056); no other associations were observed.DiscussionAs previously reported,<a class="elsevierStyleCrossRef" href="#bib0120">9</a> almost 75% of PICU-admitted patients in our study received at least one antimicrobial. PICU AU represented around 13% of total hospital AU, with a density of AU 1.4 times higher than that of the rest of hospital areas. Data evaluating the impact of PICU AU on total hospital AU are lacking.<a class="elsevierStyleCrossRef" href="#bib0095">4</a> Most pediatric studies report either global hospital AU, or PICU AU alone.<a class="elsevierStyleCrossRefs" href="#bib0085">2–4</a> Our density of AU is lower than that in adult ICUs,<a class="elsevierStyleCrossRef" href="#bib0115">8</a> which has been reported to be 2.2–3 times higher than in non-ICU areas,<a class="elsevierStyleCrossRef" href="#bib0115">8</a> but it still represents a major portion of total hospital AU. This highlights how important it is for ASP to work together with PICU teams.<a class="elsevierStyleCrossRef" href="#bib0085">2</a> Studies on PICU AU are scarce and difficult to compare, mainly due to differences in the indicators used, levels of care, areas of specialization, and the local antimicrobial resistance patterns.<a class="elsevierStyleCrossRefs" href="#bib0090">3,9,10</a>Although many authors have recommended the use of more than one indicator when reporting AU data, most PICU studies are based on standardized DOT alone.<a class="elsevierStyleCrossRef" href="#bib0095">4</a> DOT have intrinsic limitations such as overrepresentation of the use of >1 antimicrobial regardless of their spectrum.<a class="elsevierStyleCrossRef" href="#bib0105">6</a> We used LOT as a complementary indicator to overcome DOT limitations. LOT gives a good picture of the overall length of antimicrobial prescriptions in a specific unit or center and, together with LOS, is usually easier to understand to prescribers than DOT.<a class="elsevierStyleCrossRef" href="#bib0130">11</a> The short LOT we observed (median 2.0 days) was likely due to the elevated proportion of prophylactic cefazolin prescriptions.<a class="elsevierStyleCrossRef" href="#bib0120">9</a>Cefazolin is known to be one of the commonest antimicrobials in PICUs.<a class="elsevierStyleCrossRefs" href="#bib0085">2,9</a> In accordance with previous studies, longer than required prophylaxis and high use of broad-spectrum antimicrobials were identified as the main causes of non-optimal prescription.<a class="elsevierStyleCrossRefs" href="#bib0125">10,12,13</a> A number of authors have demonstrated that ASP can successfully reduce the use of the latter, which in turn can have a relevant impact on antimicrobial resistance rates.<a class="elsevierStyleCrossRefs" href="#bib0100">5,9</a> In our study, piperacillin-tazobactam and meropenem represented 7.8% and 6.1% of total AU during 2019, respectively. Except for the August peak, these rates are lower than those reported by PICUs similar to ours, in terms of patients’ complexity and conditions treated, in the absence of ASP, which range from 14.3% to 31.5%.<a class="elsevierStyleCrossRefs" href="#bib0135">12,13</a>RR and MR remained low and stable during the study period<a class="elsevierStyleCrossRef" href="#bib0145">14</a>; suggesting that ASP interventions did not lead to increased harm.<a class="elsevierStyleCrossRefs" href="#bib0080">1,5,7</a> In August 2019, the rise in broad-spectrum AU, LOS, and MR was accompanied by a drop in the QP rate. This can be partly explained both by the increased complexity of the patients’ conditions, and a decline in the number of admissions after elective surgeries during the summer period. Permanent monitoring by ASP teams can help detect unexpected variations in ASP indicators, allowing for implementation of corrective measures.<a class="elsevierStyleCrossRef" href="#bib0110">7</a>QP monitoring is time-consuming and further complicates standardization due to the different QP indicators available.<a class="elsevierStyleCrossRefs" href="#bib0080">1,13</a> However, it should be kept in mind that the main objective of ASP is to improve quality of care, above decreasing AU or expenditure.<a class="elsevierStyleCrossRefs" href="#bib0110">7,13</a> Compared to previous studies, our QP rates were high<a class="elsevierStyleCrossRefs" href="#bib0125">10,13</a>; nevertheless, some areas for improvement were identified, such as shortening prophylactic courses and de-escalating broad-spectrum antimicrobial regimens. The former can be achieved by means of biomarker-based decision algorithms, tailoring the duration of antibiotics to the intraoperative findings, automated e-prescription filters for certain drugs, or the implementation of periodical rounds with infectious diseases specialists and pharmacists.<a class="elsevierStyleCrossRef" href="#bib0150">15</a>The single-center observational design, the short study period, and the lack of previous data for comparison are obvious limitations of our study. ASP evaluations should be complemented with microbiological indicators (i.e. extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae, multi-drug resistant Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus) in the search for changes in resistance patterns. Finally, PPS do not allow to draw conclusions about data outside the specified time frame.In summary, our study shows the relevant impact of PICU AU on the global hospital AU, although the density of use was lower than that reported in adult ICUs. A high rate of optimal prescriptions was observed, but unnecessary broad-spectrum regimens and longer than required prophylaxis were identified. Available data on PICU AU are scarce and heterogeneous, making comparisons difficult to establish. Appropriate ASP indicators for PICU patients are needed to establish targets, assess the impact of interventions, and permit benchmarking.FundingNo specific funding was received for this study; data were generated as part of the routine work of Hospital Sant Joan de Déu.Conflicts of interestSílvia Simó Nebot was supported by “Contratos Río Hortega, Convocatoria 2018” (Acción Estratégica de Salud, Ayudas y Subvenciones, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain) [CM18/00054]. Antoni Noguera-Julian was supported by “Subvencions per a la Intensificació de Facultatius Especialistes” (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016–2020) [SLT008/18/00193].Sílvia Simó Nebot and Clàudia Fortuny have received funds for speaking at symposia organized on behalf of Gilead Sciences.The rest of the authors have no conflicts of interest to disclose." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1657796" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1473416" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1473417" "titulo" => "Abbreviations" ] 3 => array:3 [ "identificador" => "xres1657797" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1473418" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Setting" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 11 => array:2 [ "identificador" => "xack584164" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-12-29" "fechaAceptado" => "2021-05-11" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1473416" "palabras" => array:5 [ 0 => "Antimicrobial stewardship" 1 => "Antimicrobial use" 2 => "Length-of-treatment" 3 => "PICU" 4 => "Prophylaxis" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1473417" "palabras" => array:13 [ 0 => "AU" 1 => "ASP" 2 => "DOT" 3 => "DP" 4 => "ICU" 5 => "IQR" 6 => "LOT" 7 => "MR" 8 => "PICU" 9 => "PPS" 10 => "PRISM III" 11 => "QP" 12 => "RR" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1473418" "palabras" => array:5 [ 0 => "Optimización de uso de antimicrobianos" 1 => "Uso de antimicrobianos" 2 => "Duración de tratamiento" 3 => "UCIP" 4 => "Profilaxis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionWe aimed to describe antimicrobial use (AU) and quality of prescriptions (QP) in a 28-bed medical-surgical PICU of a European referral children's hospital during 2019. MethodsAU data were expressed as days-of-therapy (DOT) over 100 days-present (DP) and as length-of-treatment (LOT). QP was based on monthly cross-sectional point-prevalence surveys. Length-of-stay (LOS), readmission rates (RR), and mortality rates (MR) were also collected. ResultsPICU AU accounted for 13.5% of the global hospital AU; the median PICU density of AU was 1.4 (IQR 1.3–1.5) times higher than that of the rest of the hospital areas. Antibacterials represented 88.5% of the overall AU, cefazolin and amoxicillin-clavulanate being the most used drugs. A high QP rate was observed (149/168 optimal, 88.9%), with room for improvement in prophylactic regimens and de-escalation of broad-spectrum regimens. LOT, LOS, RR, and MR remained stable. ConclusionsPICU AU represented a major portion of the global hospital AU. Despite high QP rates, prophylactic and broad-spectrum antibiotic regimens were optimizable." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónSe describe el uso de antimicrobianos (AU) y la calidad de las prescripciones (QP) durante 2019 de una UCI pediátrica médico-quirúrgica de 28 camas de un hospital infantil europeo de tercer nivel. MétodosEl AU se expresó en días de tratamiento (DOT) por 100 días-presente (DP) y en duración de tratamiento (LOT). La QP se midió en cortes mensuales. Asimismo, se recogieron datos sobre duración de ingreso (LOS), tasas de reingreso (RR) y tasas de mortalidad (MR). ResultadosEl AU de la UCI pediátrica representó el 13,5% del AU global del centro y la densidad media de AU fue 1,4 (RIC 1,3-1,5) veces mayor que la del resto de áreas hospitalarias. Los antibacterianos representaron el 88,5% del total de AU, siendo cefazolina y amoxicilina-clavulánico los fármacos más utilizados. Se observó una tasa elevada de prescripciones óptimas (149/168; 88,9%), con margen de mejora en las profilaxis y el desescalado de tratamientos de amplio espectro. LOT, LOS, RR y MR se mantuvieron estables. ConclusionesLa UCI pediátrica representó una parte importante del AU global hospitalario. A pesar de la elevada QP global, los regímenes antibióticos profilácticos y de amplio espectro resultaron optimizables." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "These authors contributed equally to the study." "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0055" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1747 "Ancho" => 1529 "Tamanyo" => 220347 ] ] "descripcion" => array:1 [ "en" => "Monthly antimicrobial use expressed in days-of-therapy over 100 days present (DOT/100DP) in PICU. (a) Global antibacterial, antiviral, and antifungal drugs use; (b) six most used antibacterials during 2019." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "AU, antimicrobial use; DOT, days-of-therapy; DP, days-present; LOS, length-of-stay; LOT, length-of-treatment; MR, mortality rates; QP, quality of prescriptions; RR, readmission rates." "tablatextoimagen" => array:1 [ 0 => array:2 [ "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AU (DOT/100DP, median) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LOT (days, median) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LOS (days, median) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RR (%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MR (%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PRISM III score (median) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QP (% of optimal prescriptions) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Evaluated prescriptions (n)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Jan. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">101.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.3 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Feb. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">114.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mar. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">101.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Apr. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">May \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.9 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">June \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">July \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">107.9 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aug. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">152.3 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sept. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77.3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oct. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100.2 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nov. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dec. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.0 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86.7 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2019 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98.6 (90.5–103.2) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.0 (2.0–3.0) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 (4.2–4.8) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.4% (0–0.9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3% (0.6–1.8) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.0 (2.8–3.6) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88.9% (81.8–90.9) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">168 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2822505.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Individual drug prescriptions; 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Monthly data are expressed as medians or proportions. Total 2019 data are expressed as medians and interquartile ranges of monthly values, or proportions and 95% confidence intervals of monthly values." ] ] 2 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 837146 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inpatient antimicrobial stewardship in pediatrics: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.J. Smith" 1 => "J.S. Gerber" 2 => "A.L. 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We also thank all the Pharmacy Department and the Pediatric Intensive Care Unit team of Hospital Sant Joan de Déu for their daily dedication to improving the management and quality of care of critically ill pediatric patients and, finally, the computer, statistics, and hospital management teams of Hospital Sant Joan de Déu and Sant Joan de Déu Research Foundation for their invaluable help in antimicrobial use data extraction and analysis." 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Brief report

Impact and quality of antimicrobial use in a referral pediatric intensive care unit

Impacto y calidad del uso de antimicrobianos en una unidad de cuidados intensivos pediátricos de referencia

Silvia Simó Nebota,b,1, María G. López-Ramosc,1, Eneritz Velasco-Arnaiza, Iolanda Jordanb,d,e,f, Clàudia Fortunya,b,d,e, Antoni Noguera-Juliana,b,d,e,

Corresponding author

ton@sjdhospitalbarcelona.org

Corresponding author.

a Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Infectious Diseases Unit, Department of Pediatrics, Institut de Recerca Sant Joan de Déu, Barcelona, Spain

b Centre for Biomedical Network Research on Epidemiology and Public Health, CIBERESP, Madrid, Spain

c Pharmacy Department, Sant Joan de Déu Hospital, Barcelona, Spain

d Red de Investigación Translacional en Infectología Pediátrica, RITIP, Madrid, Spain

e Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain

f Pediatric Intensive Care Unit, Sant Joan de Déu Hospital, Barcelona, Spain

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        "titulo" => "Impacto y calidad del uso de antimicrobianos en una unidad de cuidados intensivos pedi&#225;tricos de referencia"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Monthly antimicrobial use expressed in days-of-therapy over 100 days present &#40;DOT&#47;100DP&#41; in PICU&#46; &#40;a&#41; Global antibacterial&#44; antiviral&#44; and antifungal drugs use&#59; &#40;b&#41; six most used antibacterials during 2019&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Antimicrobial use &#40;AU&#41; is high in the pediatric population&#44; especially among pediatric intensive care unit &#40;PICU&#41; patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;2</span></a> PICU patients are at risk of healthcare-associated infections&#44; many of which are caused by resistant microorganisms that require broad-spectrum antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> PICUs also account for a high use of prophylactic antimicrobials&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#44;3</span></a> Antimicrobial stewardship programs &#40;ASP&#41; have proved their effectiveness in reducing AU in children&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;4&#44;5</span></a> but data on the most effective interventions for children and&#44; especially&#44; for the critically ill pediatric population remain limited&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;4</span></a> Moreover&#44; the use of classical AU measures in adults&#44; such as &#8220;defined daily dose&#8221;&#44; is discouraged in children because of the weight-based dosage of antimicrobials in this population&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Data about the impact of PICU AU on the total hospital AU are lacking&#44; although AU density could be up to three times higher than in ward units according to adult experience&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> Also&#44; very few studies have reported on ASP experiences in improving PICU quality of prescriptions &#40;QP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We aimed to describe AU and QP in a referral pediatric PICU and their impact on total hospital AU during the year 2019&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Setting</span><p id="par0020" class="elsevierStylePara elsevierViewall">We conducted a prospective observational study during 2019 in the 28-bed medical-surgical PICU of Hospital Sant Joan de D&#233;u &#40;Barcelona&#44; Spain&#41;&#44; a 268-pediatric-bed referral hospital with a full range of medical and surgical specialties and a 4-bed bone marrow transplant unit&#46; The yearly number of hospital and PICU discharges are around 15&#44;000 and 1200&#44; respectively&#59; among the latter&#44; approximately 45&#37; correspond to surgical patients &#40;neurosurgery and cardiac surgery&#44; one third each&#41;&#46; A median of 6 extracorporeal membrane oxygenation procedures are performed yearly&#46; The median Pediatric Risk of Mortality III score &#40;PRISM III&#41; for PICU-admitted patients in 2019 was 3&#46;0 &#40;IQR 2&#46;8&#8211;3&#46;6&#41;&#46; The fully operational hospital ASP was implemented in January 2017&#46; The main ASP strategy was face-to-face and&#47;or electronic post-prescription review with feedback&#44; together with other non-restrictive and educational strategies &#40;see Suppl&#46; Appendix 1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> This study was approved by the local ethics committee &#40;ref&#46; 32&#8211;20&#41;&#44; which granted a waiver of individual informed consent&#46; The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Design</span><p id="par0025" class="elsevierStylePara elsevierViewall">Data were collected from the e-prescription system and electronic clinical charts between January 1 and December 31&#44; 2019&#46; AU was calculated using days-of-therapy &#40;DOT&#41;&#44; defined as the aggregate sum of days that a specific antimicrobial was administered to a patient&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5&#44;9</span></a> To express density of AU&#44; DOT was standardized to 100 days present &#40;DP&#41;&#44; considering one day present any amount of time in a calendar day spent by a patient in a definite hospital location&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> Length-of-therapy &#40;LOT&#41; was used as a complementary AU indicator and defined as the duration of antimicrobial treatment in days&#46; All systemic antibacterials&#44; antifungals&#44; and antivirals were included&#46; Other complementary measures included length-of-stay &#40;LOS&#41;&#44; PICU readmission rates during the hospital admission &#40;RR&#41; and mortality rates within PICU admission &#40;MR&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">QP was recorded based on monthly cross-sectional point-prevalence surveys &#40;PPS&#41; during which all the prescriptions for PICU patients were evaluated&#46; For a prescription to be considered &#8216;optimal&#8217; the prescribed drug should follow local reference guidelines accounting for patient allergies&#44; and should be administered through the correct route&#44; dose&#44; and schedule&#44; and for an appropriate duration &#40;considering the actual duration or the expected duration recorded in the e-prescription system or in the patient medical record&#59; Suppl&#46; Appendix 1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Categorical variables were reported as proportions with 95&#37; confidence intervals&#44; and continuous variables as medians with interquartile ranges &#40;IQRs&#41;&#46; Correlation between variables was calculated using Pearson&#39;s correlation coefficient&#46; Statistical analysis was carried out using SPSS version 25&#46;0 software &#40;IBM Corp&#46;&#44; Armonk&#44; NY&#44; U&#46;S&#46;A&#46;&#41;&#46; Statistical significance was defined as a <span class="elsevierStyleItalic">p</span>-value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">During 2019&#44; 966 out of 1302 &#40;74&#46;2&#37;&#41; patients admitted in the PICU received antimicrobials&#46; The PICU AU represented 13&#46;5&#37; of the global hospital AU during 2019 &#40;PICU and all hospital areas absolute DOT&#58; 6827 and 50&#44;666&#44; respectively&#41;&#46; PICU presented a median density of AU 1&#46;4 &#40;IQR 1&#46;3&#8211;1&#46;5&#41; times higher than that of the rest of hospital areas&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Of the annual PICU AU&#44; 88&#46;5&#37; corresponded to antibacterials&#44; 5&#46;8&#37; to antivirals&#44; and 5&#46;7&#37; to antifungals &#40;see <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> and Suppl&#46; Table 1&#41;&#46; The parenteral route prevailed &#40;82&#46;1&#37;&#41;&#46; Year 2019 most frequently used antibiotics were cefazolin &#40;183&#46;6 DOT&#47;100DP&#44; 15&#46;3&#37;&#41;&#44; amoxicillin-clavulanate &#40;127&#46;6 DOT&#47;100DP&#44; 10&#46;6&#37;&#41;&#44; vancomycin &#40;126&#46;2 DOT&#47;100DP&#44; 10&#46;5&#37;&#41;&#44; and cefotaxime &#40;102&#46;1 DOT&#47;100DP&#44; 8&#46;5&#37;&#41;&#46; Acyclovir &#40;30&#46;8 DOT&#47;100DP&#44; 2&#46;6&#37;&#41; and liposomal amphotericin B &#40;21&#46;2 DOT&#47;100DP&#44; 1&#46;8&#37;&#41; were the most commonly used antiviral and antifungal drugs&#44; respectively&#46; Main results expressed in monthly medians are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding QP&#44; 168 antimicrobial prescriptions for 95 patients were evaluated in the 12 monthly PPS&#44; 20&#46;8&#37; of which had a prophylactic intention &#40;see Suppl&#46; Table 2&#41;&#46; High rates of optimal prescriptions were observed in all PPS &#40;median 88&#46;9&#37;&#44; IQR 81&#46;8&#8211;90&#46;9&#41; except in August &#40;57&#46;1&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The most frequent reasons for non-optimal prescription &#40;19&#47;168&#44; 11&#46;3&#37;&#41; were an inadequate spectrum &#40;9&#47;19&#44; excessively broad and too narrow spectrum in 7 and 2&#44; respectively&#41; and excessive antimicrobial course duration &#40;7&#47;19&#41;&#46; Nearly one third &#40;30&#46;0&#37;&#41; of non-optimal prescriptions had a prophylactic intention&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In August 2019&#44; due to an increase in critically ill patients with hematological malignancies&#44; meropenem&#44; piperacillin-tazobactam&#44; and vancomycin use peaked&#44; together with an increase in LOS and MR and a marked decrease in QP &#40;see <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Other than this&#44; LOT&#44; LOS&#44; RR&#44; and MR remained stable during 2019 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; DOT and QP rates inversely correlated &#40;Pearson&#39;s correlation&#59; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;565&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;056&#41;&#59; no other associations were observed&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">As previously reported&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> almost 75&#37; of PICU-admitted patients in our study received at least one antimicrobial&#46; PICU AU represented around 13&#37; of total hospital AU&#44; with a density of AU 1&#46;4 times higher than that of the rest of hospital areas&#46; Data evaluating the impact of PICU AU on total hospital AU are lacking&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Most pediatric studies report either global hospital AU&#44; or PICU AU alone&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#8211;4</span></a> Our density of AU is lower than that in adult ICUs&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> which has been reported to be 2&#46;2&#8211;3 times higher than in non-ICU areas&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> but it still represents a major portion of total hospital AU&#46; This highlights how important it is for ASP to work together with PICU teams&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> Studies on PICU AU are scarce and difficult to compare&#44; mainly due to differences in the indicators used&#44; levels of care&#44; areas of specialization&#44; and the local antimicrobial resistance patterns&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3&#44;9&#44;10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Although many authors have recommended the use of more than one indicator when reporting AU data&#44; most PICU studies are based on standardized DOT alone&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> DOT have intrinsic limitations such as overrepresentation of the use of &#62;1 antimicrobial regardless of their spectrum&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> We used LOT as a complementary indicator to overcome DOT limitations&#46; LOT gives a good picture of the overall length of antimicrobial prescriptions in a specific unit or center and&#44; together with LOS&#44; is usually easier to understand to prescribers than DOT&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> The short LOT we observed &#40;median 2&#46;0 days&#41; was likely due to the elevated proportion of prophylactic cefazolin prescriptions&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Cefazolin is known to be one of the commonest antimicrobials in PICUs&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#44;9</span></a> In accordance with previous studies&#44; longer than required prophylaxis and high use of broad-spectrum antimicrobials were identified as the main causes of non-optimal prescription&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10&#44;12&#44;13</span></a> A number of authors have demonstrated that ASP can successfully reduce the use of the latter&#44; which in turn can have a relevant impact on antimicrobial resistance rates&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5&#44;9</span></a> In our study&#44; piperacillin-tazobactam and meropenem represented 7&#46;8&#37; and 6&#46;1&#37; of total AU during 2019&#44; respectively&#46; Except for the August peak&#44; these rates are lower than those reported by PICUs similar to ours&#44; in terms of patients&#8217; complexity and conditions treated&#44; in the absence of ASP&#44; which range from 14&#46;3&#37; to 31&#46;5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">RR and MR remained low and stable during the study period<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a>&#59; suggesting that ASP interventions did not lead to increased harm&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;5&#44;7</span></a> In August 2019&#44; the rise in broad-spectrum AU&#44; LOS&#44; and MR was accompanied by a drop in the QP rate&#46; This can be partly explained both by the increased complexity of the patients&#8217; conditions&#44; and a decline in the number of admissions after elective surgeries during the summer period&#46; Permanent monitoring by ASP teams can help detect unexpected variations in ASP indicators&#44; allowing for implementation of corrective measures&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">QP monitoring is time-consuming and further complicates standardization due to the different QP indicators available&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;13</span></a> However&#44; it should be kept in mind that the main objective of ASP is to improve quality of care&#44; above decreasing AU or expenditure&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">7&#44;13</span></a> Compared to previous studies&#44; our QP rates were high<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10&#44;13</span></a>&#59; nevertheless&#44; some areas for improvement were identified&#44; such as shortening prophylactic courses and de-escalating broad-spectrum antimicrobial regimens&#46; The former can be achieved by means of biomarker-based decision algorithms&#44; tailoring the duration of antibiotics to the intraoperative findings&#44; automated e-prescription filters for certain drugs&#44; or the implementation of periodical rounds with infectious diseases specialists and pharmacists&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The single-center observational design&#44; the short study period&#44; and the lack of previous data for comparison are obvious limitations of our study&#46; ASP evaluations should be complemented with microbiological indicators &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span> extended spectrum beta-lactamase and carbapenemase producing <span class="elsevierStyleItalic">Enterobacteriaceae</span>&#44; multi-drug resistant <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> or methicillin resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#41; in the search for changes in resistance patterns&#46; Finally&#44; PPS do not allow to draw conclusions about data outside the specified time frame&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In summary&#44; our study shows the relevant impact of PICU AU on the global hospital AU&#44; although the density of use was lower than that reported in adult ICUs&#46; A high rate of optimal prescriptions was observed&#44; but unnecessary broad-spectrum regimens and longer than required prophylaxis were identified&#46; Available data on PICU AU are scarce and heterogeneous&#44; making comparisons difficult to establish&#46; Appropriate ASP indicators for PICU patients are needed to establish targets&#44; assess the impact of interventions&#44; and permit benchmarking&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0095" class="elsevierStylePara elsevierViewall">No specific funding was received for this study&#59; data were generated as part of the routine work of Hospital Sant Joan de D&#233;u&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">S&#237;lvia Sim&#243; Nebot was supported by &#8220;Contratos R&#237;o Hortega&#44; Convocatoria 2018&#8221; &#40;Acci&#243;n Estrat&#233;gica de Salud&#44; Ayudas y Subvenciones&#44; Instituto de Salud Carlos III&#44; Ministerio de Ciencia e Innovaci&#243;n&#44; Spain&#41; &#91;CM18&#47;00054&#93;&#46; Antoni Noguera-Julian was supported by &#8220;Subvencions per a la Intensificaci&#243; de Facultatius Especialistes&#8221; &#40;Departament de Salut de la Generalitat de Catalunya&#44; Programa PERIS 2016&#8211;2020&#41; &#91;SLT008&#47;18&#47;00193&#93;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">S&#237;lvia Sim&#243; Nebot and Cl&#224;udia Fortuny have received funds for speaking at symposia organized on behalf of Gilead Sciences&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The rest of the authors have no conflicts of interest to disclose&#46;</p></span></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We aimed to describe antimicrobial use &#40;AU&#41; and quality of prescriptions &#40;QP&#41; in a 28-bed medical-surgical PICU of a European referral children&#39;s hospital during 2019&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">AU data were expressed as days-of-therapy &#40;DOT&#41; over 100 days-present &#40;DP&#41; and as length-of-treatment &#40;LOT&#41;&#46; QP was based on monthly cross-sectional point-prevalence surveys&#46; Length-of-stay &#40;LOS&#41;&#44; readmission rates &#40;RR&#41;&#44; and mortality rates &#40;MR&#41; were also collected&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">PICU AU accounted for 13&#46;5&#37; of the global hospital AU&#59; the median PICU density of AU was 1&#46;4 &#40;IQR 1&#46;3&#8211;1&#46;5&#41; times higher than that of the rest of the hospital areas&#46; Antibacterials represented 88&#46;5&#37; of the overall AU&#44; cefazolin and amoxicillin-clavulanate being the most used drugs&#46; A high QP rate was observed &#40;149&#47;168 optimal&#44; 88&#46;9&#37;&#41;&#44; with room for improvement in prophylactic regimens and de-escalation of broad-spectrum regimens&#46; LOT&#44; LOS&#44; RR&#44; and MR remained stable&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">PICU AU represented a major portion of the global hospital AU&#46; Despite high QP rates&#44; prophylactic and broad-spectrum antibiotic regimens were optimizable&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se describe el uso de antimicrobianos &#40;AU&#41; y la calidad de las prescripciones &#40;QP&#41; durante 2019 de una UCI pedi&#225;trica m&#233;dico-quir&#250;rgica de 28 camas de un hospital infantil europeo de tercer nivel&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El AU se expres&#243; en d&#237;as de tratamiento &#40;DOT&#41; por 100 d&#237;as-presente &#40;DP&#41; y en duraci&#243;n de tratamiento &#40;LOT&#41;&#46; La QP se midi&#243; en cortes mensuales&#46; Asimismo&#44; se recogieron datos sobre duraci&#243;n de ingreso &#40;LOS&#41;&#44; tasas de reingreso &#40;RR&#41; y tasas de mortalidad &#40;MR&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">El AU de la UCI pedi&#225;trica represent&#243; el 13&#44;5&#37; del AU global del centro y la densidad media de AU fue 1&#44;4 &#40;RIC 1&#44;3-1&#44;5&#41; veces mayor que la del resto de &#225;reas hospitalarias&#46; Los antibacterianos representaron el 88&#44;5&#37; del total de AU&#44; siendo cefazolina y amoxicilina-clavul&#225;nico los f&#225;rmacos m&#225;s utilizados&#46; Se observ&#243; una tasa elevada de prescripciones &#243;ptimas &#40;149&#47;168&#59; 88&#44;9&#37;&#41;&#44; con margen de mejora en las profilaxis y el desescalado de tratamientos de amplio espectro&#46; LOT&#44; LOS&#44; RR y MR se mantuvieron estables&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La UCI pedi&#225;trica represent&#243; una parte importante del AU global hospitalario&#46; A pesar de la elevada QP global&#44; los reg&#237;menes antibi&#243;ticos profil&#225;cticos y de amplio espectro resultaron optimizables&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">These authors contributed equally to the study&#46;</p>"
        "identificador" => "fn0005"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0125" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0055"
          ]
        ]
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1747
            "Ancho" => 1529
            "Tamanyo" => 220347
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Monthly antimicrobial use expressed in days-of-therapy over 100 days present &#40;DOT&#47;100DP&#41; in PICU&#46; &#40;a&#41; Global antibacterial&#44; antiviral&#44; and antifungal drugs use&#59; &#40;b&#41; six most used antibacterials during 2019&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">AU&#44; antimicrobial use&#59; DOT&#44; days-of-therapy&#59; DP&#44; days-present&#59; LOS&#44; length-of-stay&#59; LOT&#44; length-of-treatment&#59; MR&#44; mortality rates&#59; QP&#44; quality of prescriptions&#59; RR&#44; readmission rates&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AU &#40;DOT&#47;100DP&#44; median&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LOT &#40;days&#44; median&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LOS &#40;days&#44; median&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RR &#40;&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MR &#40;&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PRISM III score &#40;median&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QP &#40;&#37; of optimal prescriptions&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Evaluated prescriptions &#40;<span class="elsevierStyleItalic">n</span>&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Jan&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">101&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#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="left" valign="\n
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                  \t\t\t\t">5&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="left" valign="\n
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                  \t\t\t\t">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="left" valign="\n
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                  \t\t\t\t">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="left" valign="\n
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                  \t\t\t\t">90&#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="char" valign="\n
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                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Feb&#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="left" valign="\n
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                  \t\t\t\t">114&#46;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="left" valign="\n
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                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#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="left" valign="\n
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                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#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="left" valign="\n
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                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mar&#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="left" valign="\n
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                  \t\t\t\t">101&#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="left" valign="\n
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                  \t\t\t\t">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="left" valign="\n
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                  \t\t\t\t">4&#46;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;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="left" valign="\n
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                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Apr&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">May&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Dec&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2019&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">98&#46;6 &#40;90&#46;5&#8211;103&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32303891"
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    "agradecimientos" => array:1 [
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        "identificador" => "xack584164"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0115" class="elsevierStylePara elsevierViewall">We would like to thank Maria R&#237;os-Barnes&#44; Manuel Monson&#237;s and Mireia Urrea of Hospital Sant Joan de D&#233;u&#8217; Antimicrobial Stewardship Program&#44; as well as Cl&#224;udia Fortuny and Franscisco Jos&#233; Cambra for their contribution to the study&#46; We also thank all the Pharmacy Department and the Pediatric Intensive Care Unit team of Hospital Sant Joan de D&#233;u for their daily dedication to improving the management and quality of care of critically ill pediatric patients and&#44; finally&#44; the computer&#44; statistics&#44; and hospital management teams of Hospital Sant Joan de D&#233;u and Sant Joan de D&#233;u Research Foundation for their invaluable help in antimicrobial use data extraction and analysis&#46;</p>"
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    "identificador" => "66624"
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      "titulo" => "Brief reports"
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    "idiomaDefecto" => "en"
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Article information

ISSN: 2529993X
Original language: English

DOI:10.1016/j.eimce.2021.05.013

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