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Assessment of a semi-automated enrichment system (Uroquattro HB&L) for detection of faecal carriers of ESBL-/AmpC-producing Enterobacterales
Evaluación de un sistema de enriquecimiento semiautomático (Uroquattro HB&L™) para la detección de portadores fecales de Enterobacterales productoras de beta-lactamasas de espectro extendido (BLEE)/AmpC
Patricia Pérez-Palaciosa, Lorena López-Cereroa,
Corresponding author
llopez@us.es

Corresponding author.
, Carmen Lupióna, Alvaro Pascuala,b
a Microbiology and Infectious Diseases Unit, University Hospital Virgen Macarena, Sevilla, Spain
b Department of Microbiology, School of Medicine of University of Seville, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Enterobacterales resistant to third-generation cephalosporins due to the acquisition of extended-spectrum beta-lactamases and plasmid-mediated cephalosporinases &#40;ESBLs&#47;pAmpC&#41; currently constitute one of the most pressing medical problems worldwide&#46; The growing dissemination of carbapenemase producers&#44; many of them also resistant to third-generation cephalosporins&#44; and the co-resistance pattern of these microorganisms represents an added problem&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> Early detection of patients carrying ESBL-&#47;pAmpC-&#47;carbapenemase-producing Enterobacterales &#40;3GCRE&#41; using surveillance cultures on admission and isolation of colonized patients is a major strategy designed to prevent the spread of resistance genes&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Recent advances in the detection of 3GCRE are based on molecular techniques or chromogenic selective media&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> Molecular techniques continue to be the gold standard due to their high&#44; almost 100&#37; sensitivity and specificity&#46; All of them are based on amplification of the main genes involved in these enzymes in 1&#8211;3<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Nevertheless&#44; the cost of molecular methods and the limited targets available restrict their systematic implementation&#46; Chromogenic selective media are the cheapest and easiest technique for detection of 3GCRE and more cost effective<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> despite their lower sensitivity &#40;around 80&#37;&#41; and the longer time taken to obtain results &#40;between 24 and 48<span class="elsevierStyleHsp" style=""></span>h&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Another strategy that improves detection of colonized patients is to add a pre-enrichment step&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> The main inconvenience of enrichment is the delay associated with obtaining results&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> The Uroquattro HB&#38;L &#40;Alifax&#174;&#41; is a new system based on a selective pre-enrichment medium and continuous measurement of growth curves using light scattering technology&#44; designed to increase the detection of third-generation cephalosporin-resistant Enterobacterales&#46; The aim of this study was to compare a selective medium routinely used in our laboratory with the semi-automated Uroquattro HB&#38;L system &#40;Alifax&#174;&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and microbiological analysis</span><p id="par0020" class="elsevierStylePara elsevierViewall">The study was performed at the University Hospital Virgen Macarena &#40;a 900-bed tertiary hospital&#41; in Seville&#44; Spain&#46; From June to October 2017&#44; consecutive double rectal swabs were collected &#40;Copan&#174;&#44; Italy&#41; from 201 inpatients included in the local surveillance programme &#40;upon ICU admission&#44; previous colonization status&#44; transfers from other centres and roommates of positive cases&#41;&#46; One swab was plated on the routinely used medium &#40;MacConkey agar supplemented with cefotaxime 4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; and incubated at 35<span class="elsevierStyleHsp" style=""></span>&#176;C for 18<span class="elsevierStyleHsp" style=""></span>h&#46; Results from routine medium were reported in 18&#8211;24<span class="elsevierStyleHsp" style=""></span>h &#40;for negative results when no growth of Enterobacterales was observed&#41; and in 48<span class="elsevierStyleHsp" style=""></span>h &#40;for negative results with growth of non 3CGRE or positive results&#41;&#46; The second swab was inoculated into the Uroquattro HB&#38;L system &#40;UHBL&#41;&#46; UHBL is a semi-automatic analyser that uses a light scattering technology to test bacteria susceptibility on rectal swabs&#46; UHBL measures the growth of bacteria in specific selective enrichment broths providing real time growth curves and bacterial counts &#40;CFU&#47;ml&#41; every hour with a specific interpretation algorithm&#46; Measurements of the growth curve were taken at 6&#46;5<span class="elsevierStyleHsp" style=""></span>h &#40;according to the manufacturer&#39;s instructions&#41; and at 10<span class="elsevierStyleHsp" style=""></span>h &#40;to assess whether longer incubation might increase detection&#41;&#46; Positive samples were subcultured in MacConkey agar containing cefotaxime &#40;4<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#41;&#46; All isolates detected by both methods were identified by MALDI-TOF &#40;Bruker&#41;&#46; Screening for ESBL or pAmpC production was performed on Mueller-Hinton agar plates with or without cloxacillin &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#41;&#44; with double discs according to the European Committee on Antimicrobial Susceptibility Testing &#40;EUCAST&#41; guidelines&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The presence of <span class="elsevierStyleItalic">bla</span> genes &#40;ESBL&#58; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">SHV</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CTX-M-1</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CTX-M-9</span>&#59; pAmpC&#58; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">MOX</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CIT</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">DHA</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">ACC</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">EBC</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY</span> and <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">FOX</span>&#59; carbapenemase&#58; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">KPC</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">NDM</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">VIM</span>&#44; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">IMP</span> and <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">OXA-48</span>&#41; was studied by PCR using specific group primers<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> and further sequencing of amplicons&#46; The reference value was the combination of obtained from both methods&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">To assess of concordant and discordant results&#44; percent agreement and the exact McNemar test were calculated &#40;SPSS Statistics&#44; version 23&#46;0&#41; for 3GCRE positives and negatives rectal swab of UHBL system at 6&#46;5 and at 10<span class="elsevierStyleHsp" style=""></span>h and the routine medium&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">A total of 35 samples &#40;17&#46;4&#37;&#41; were positive for 3GCRE&#46; <span class="elsevierStyleItalic">E&#46; coli</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41; was the most prevalent microorganism &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Among ESBL enzymes&#44; the most frequent was CTX-M-15 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#44; 37&#46;8&#37;&#41;&#59; pAmpC &#40;CMY-2&#41; and carbapenemases &#40;KPC-2 and VIM-1&#41; were also found &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Measurements of the UHBL system at 6&#46;5<span class="elsevierStyleHsp" style=""></span>h and 10<span class="elsevierStyleHsp" style=""></span>h were compared to direct culture on solid medium for all 3GCRE positive and negative cultures &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Thirty-five rectal swabs were positive for 3GCRE for both UHBL system and routine medium&#44; whereas 4 and 7 rectal swabs were positive only with UHBL system at 6&#46;5<span class="elsevierStyleHsp" style=""></span>h and 10<span class="elsevierStyleHsp" style=""></span>h&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Measurements at 10<span class="elsevierStyleHsp" style=""></span>h incremented a 5&#46;7&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 1&#46;5&#8211;1&#46;8&#37;&#41; &#40;2&#47;35&#41; the positive 3GCRE detection in comparison with the routine culture medium&#46; The increments of false positive results were 1&#46;2&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 0&#46;3&#8211;0&#46;4&#37;&#41; &#40;2&#47;166&#41;&#44; and 7&#46;2&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 4&#46;1&#8211;12&#46;2&#37;&#41; &#40;12&#47;166&#41;&#44; at 6&#46;5<span class="elsevierStyleHsp" style=""></span>h and 10<span class="elsevierStyleHsp" style=""></span>h&#44; respectively&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">Active screening cultures to prevent nosocomial infections and outbreaks are performed in many hospitals&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> although an optimal screening protocol has not yet been established&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> The present study evaluates for the first time a semi-automated screening system&#44; the Uroquattro HB&#38;L&#44; which provides early and higher detection of faecal carriers of ESBL-&#47;pAmpC-&#47;carbapenemase-producing Enterobacterales&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">There are two aspects of carrier detection surveillance that are fundamental&#58; firstly&#44; the accuracy of the method and secondly&#44; the time to detection&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> The use of a pre-enrichment step increases the detection efficiency in comparison to the usual strategy of inoculating samples directly onto selective solid media&#44; at the expenses of longer detection time and higher false positive rates&#46; The results obtained in a previous study comparing solid and pre-enrichment cultures<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> found an agreement in negative samples of 96&#46;8&#37;&#44; consistent with our results&#46; Previous studies yielded higher increases of detection with the enrichment &#40;25&#46;9&#37;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> and 20&#37;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> compared with 5&#46;7&#37; in our study&#41; and lower increases of false positive rates &#40;2&#46;1&#37;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> and 0&#46;5&#37;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> compared with our study&#41;&#44; taken into account lower prevalence of ESBL producer positive patients &#40;4&#46;8&#37;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> and 9&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> compared to 18&#46;4&#37; in our study&#41;&#46; The variation between the yield and the false positive rate with pre-enrichment&#44; may increase when the prevalence of ESBL&#47;AmpC carriers rise&#46; Rectal swabs negative by direct culture and positive by enrichment may be due to low bacterial loads&#44; which may have less epidemiological relevance&#44; although these bacterial loads may variate depending on time of hospitalization and antibiotic exposure&#46; Selection of previous detected ESBL producers have been seen in patients with negative samples without enrichment upon admission of the ICU&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> Follow-up studies are necessary to establish the risk of transmission according to faecal load&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Uroquattro HB&#38;L system reduces the time of detection to 6&#46;5<span class="elsevierStyleHsp" style=""></span>h&#44; according to the manufacturer&#44; although an increment in detection was obtained at 10<span class="elsevierStyleHsp" style=""></span>h according to our results&#46; Nevertheless&#44; both 6&#46;5<span class="elsevierStyleHsp" style=""></span>h and 10<span class="elsevierStyleHsp" style=""></span>h enable the characterization of 3CGRE to begin on the same day that the sample is received and&#44; a more important issue&#44; shortening the time for negative results&#46; Earlier detection could have an impact on costs&#46; Sypsa et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> using a mathematical model&#44; concluded that a delay in detection&#44; even by one day&#44; increased the costs associated with outbreaks&#46; On the other hand&#44; an earlier negative result may have an impact by reducing the adverse effects of isolation&#44; such as supportive care failures due less time spent by health workers or patient mental problems&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Molecular methods could reduce even more the result time&#44; but a higher cost&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">This study had limitations&#46; In our study we used the Copan Transystem&#8482; swabs with Amies solid medium&#44; while the manufacturer of the semi-automated system recommends the use of nylon-flocked swabs with Amies liquid &#40;ESwab&#41;&#46; However&#44; not all hospitals have introduced the use of the ES-swab&#174;&#44; and our results could be valid in these situations&#46; Another limitation is that we did not inoculated the rectal swabs on blood agar as a control of enteric microbiota&#46; In addition&#44; this system does not detect OXA-48 producers not co-producing ESBL&#47;AmpC&#44; but the prevalence of infections due to these microorganisms is very low in our area&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion&#44; the use of a preenrichment semi-automatic system Uroquattro HB&#38;L in rectal swabs improved the detection of ESBL&#47;pAmpC faecal carriers with an incubation time of 10<span class="elsevierStyleHsp" style=""></span>h&#44; shortening the reporting time of negative results&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This work was partially supported by <span class="elsevierStyleGrantSponsor" id="gs1">Plan Nacional de I&#43;D&#43;i 2013&#8211;2016</span> and <span class="elsevierStyleGrantSponsor" id="gs2">Instituto de Salud Carlos III&#44; subdirecci&#243;n General de Redes y Centros de Investigaci&#243;n Cooperativa&#44; Ministerio de Econom&#237;a&#44; Industria y Competitividad&#44; Spanish Network for Research in Infectious Diseases</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs2">RD16&#47;0016&#47;0001</span>&#41; co-financed by <span class="elsevierStyleGrantSponsor" id="gs3">European Development Regional Fund</span> &#8220;A way to achieve Europe&#8221;&#44; Operative program Intelligent Growth 2014&#8211;2020&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2019-09-09"
    "fechaAceptado" => "2019-11-04"
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            0 => "ESBL"
            1 => "p<span class="elsevierStyleItalic">AmpC</span>"
            2 => "Third generation cephalosporins resistance"
            3 => "Enrichment"
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            1 => "p<span class="elsevierStyleItalic">AmpC</span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Early detection of patients carrying multiresistant bacteria is an effective implement in surveillance programs&#46; Our objective was to compare the semi-automatic Uroquattro HB&#38;L &#8220;ESBL&#47;AmpC Screening&#8221; &#40;Alifax&#174;&#41; system with the routine culture on selective media to detect ESBL&#47;pAmpC-producing microorganisms &#40;3CGRE&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 201 rectal swabs samples were processed by inoculating them into the Uroquattro HB&#38;L system&#44; performing growth curve measurements at 6&#46;5 and 10<span class="elsevierStyleHsp" style=""></span>h&#44; and into direct culture medium&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty-five samples yielded 3CGRE&#46; Measurements at 10<span class="elsevierStyleHsp" style=""></span>h incremented the positive 3GCRE detection 5&#46;7&#37; in comparison with routine culture medium&#46; In negative rectal swabs&#44; the overall percent agreement at 6&#46;5<span class="elsevierStyleHsp" style=""></span>h and 10<span class="elsevierStyleHsp" style=""></span>h <span class="elsevierStyleItalic">versus</span> routine culture medium was 93&#37; and 90&#37;&#44; respectively&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The Uroquattro HB&#38;L system increased the detection of ESBL&#47;pAmpC-producing bacteria compared to direct plating with an incubation time of 10<span class="elsevierStyleHsp" style=""></span>h and shortens the time to report a negative sample&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La detecci&#243;n temprana de pacientes portadores de bacterias multirresistentes es una medida eficaz de los programas de vigilancia&#46; Nuestro objetivo fue comparar el sistema semiautom&#225;tico Uroquattro HB&#38;L&#8482; &#171;ESBL&#47;<span class="elsevierStyleItalic">AmpC</span><span class="elsevierStyleItalic">screening</span>&#187; &#40;Alifax&#174;&#41; frente al cultivo habitual en medios selectivos para detectar microorganismos productores de beta-lactamasas de espectro extendido &#40;BLEE&#41;&#47;AmpC &#40;3CGRE&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se procesaron 201 frotis rectales mediante inoculaci&#243;n en el sistema Uroquattro HB&#38;L&#8482;&#44; se midi&#243; el crecimiento a las 6&#44;5 y 10<span class="elsevierStyleHsp" style=""></span>h&#44; y en el medio de cultivo directo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Treinta y cinco muestras fueron positivas para 3CGRE&#46; La lectura a las 10<span class="elsevierStyleHsp" style=""></span>h increment&#243; la detecci&#243;n un 5&#44;7&#37; en comparaci&#243;n con el medio habitual&#46; En muestras rectales negativas&#44; la concordancia de la lectura global a las 6&#44;5 y 10<span class="elsevierStyleHsp" style=""></span>h con el medio de cultivo habitual fue del 93 y 90&#37;&#44; respectivamente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El sistema Uroquattro HB&#38;L&#8482; increment&#243; la detecci&#243;n de bacterias productoras de BLEE&#47;pAmpC en comparaci&#243;n con el cultivo directo con un tiempo de incubaci&#243;n de 10<span class="elsevierStyleHsp" style=""></span>h y acorta los tiempos de detecci&#243;n de muestras negativas&#46;</p></span>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">1 rectal swab<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E&#46; coli</span> &#40;CTX-M-15<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CMY-2&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">1 rectal swab<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E&#46; coli</span> &#40;CTX-M-14&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">K&#46; oxytoca</span> &#40;CTX-M-14&#41;&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">1 rectal swab<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E&#46; gergoviae</span> &#40;KPC-2<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>SHV-12&#41;&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">1 rectal swab<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E&#46; coli</span> &#40;CTX-M-15&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">K&#46; pneumoniae</span> &#40;CTX-M-14&#41;&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">2 rectal swabs<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E&#46; coli</span> &#40;CTX-M-14&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">K&#46; pneumoniae</span> &#40;CTX-M-15&#41;&#46;</p>"
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">&#40;12&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2390856.png"
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0045"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">K&#46; pneumoniae</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; <span class="elsevierStyleItalic">K&#46; oxytoca</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0050"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010"><span class="elsevierStyleItalic">E&#46; cloacae</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#44; <span class="elsevierStyleItalic">E&#46; gergoviae</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44; <span class="elsevierStyleItalic">E&#46; hormachei</span> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0055"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">1 rectal swab<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E&#46; coli</span> &#40;CTX-M-15<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CTX-M-14&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">K&#46; pneumoniae</span> &#40;CTX-M-14&#41;&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Distribution of Enterobacterales and enzymes among the 35 positive rectal swabs&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Positive results were considered the detection of ESBL&#47;pAmpC producers&#46; Negative results were considered lack of growth or growth of third-generation cephalosporins resistant Gram-negative but not ESBL&#47;pAmpC producers&#46;</p>"
          "tablatextoimagen" => array:2 [
            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">&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  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">UHBL results</th></tr><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">&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  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46; of 3CGRE positive samples</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46; of 3CGRE negative samples</th></tr><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">&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  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">At 6&#46;5<span class="elsevierStyleHsp" style=""></span>h</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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results with routine culture medium&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">Positive<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&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">Negative<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&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">Positive<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&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">Negative<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\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">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="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><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">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&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">Negative&nbsp;\t\t\t\t\t\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">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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><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">155&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2390854.png"
              ]
            ]
            1 => 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">&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  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">At 10<span class="elsevierStyleHsp" style=""></span>h</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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results with routine culture medium&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">Positive<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a>&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">Negative<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a>&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">Positive<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">d</span></a>&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">Negative<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">d</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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\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">23&nbsp;\t\t\t\t\t\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">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">2&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"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\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&nbsp;\t\t\t\t\t\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">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2390855.png"
              ]
            ]
          ]
          "notaPie" => array:5 [
            0 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Overall percent agreement&#44; 45&#46;7&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 30&#46;4&#8211;61&#46;8&#37;&#41;&#59; exact McNemar test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;74&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Overall percent agreement&#44; 93&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 89&#46;2&#8211;96&#46;7&#37;&#41;&#59; exact McNemar test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Overall percent agreement&#44; 65&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 49&#46;1&#8211;79&#46;1&#37;&#41;&#59; exact McNemar test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;77&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Overall percent agreement&#44; 90&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 84&#46;2&#8211;93&#46;9&#37;&#41;&#59; exact McNemar test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#46;</p>"
            ]
            4 => array:3 [
              "identificador" => "tblfn0040"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0040">UHBL&#58; Uroquattro HB&#38;L system&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Comparison of the UHBL<a class="elsevierStyleCrossRef" href="#tblfn0040">&#42;</a> system at 6&#46;5<span class="elsevierStyleHsp" style=""></span>h and 10<span class="elsevierStyleHsp" style=""></span>h with the routine culture medium&#46;</p>"
        ]
      ]
    ]
    "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" => "AmpC disk test for detection of plasmid-mediated AmpC &#946;-lactamases in Enterobacteriaceae lacking chromosomal AmpC &#946;-lactamases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;A&#46; Black"
                            1 => "E&#46;S&#46; Moland"
                            2 => "K&#46;S&#46; Thomson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.43.7.3110-3113.2005"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2005"
                        "volumen" => "43"
                        "paginaInicial" => "3110"
                        "paginaFinal" => "3113"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16000421"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical impact and relevance of antibiotic resistance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "G&#46;L&#46; French"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.addr.2005.04.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Drug Deliv Rev"
                        "fecha" => "2005"
                        "volumen" => "57"
                        "paginaInicial" => "1514"
                        "paginaFinal" => "1527"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15978698"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos