Brief report
Evaluation of three commercial methods of susceptibility testing for ceftolozane/tazobactam against carbapenem-resistant Pseudomonas aeruginosa
Evaluación de 3 métodos comerciales de determinación de sensibilidad de ceftolozano/tazobactam frente a Pseudomonas aeruginosa resistente a las carbapenemas
Lorena López-Cereroa,b,c,d,
, Sofia Ballestab,c, Cristina Elías Lópeze, Waldo Sánchez-Yebraf, María Dolores Rojo-Marting, Alvaro Pascuala,b,c,d
Corresponding author
a Unidad de Gestión Clínica de Microbiología y Enfermedades infecciosas, Hospital Virgen Macarena, Sevilla, Spain
b Departamento de Microbiología, Facultad de Medicina de Sevilla, Sevilla, Spain
c Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen Macarena/CSIC/Universidad de Sevilla, Spain
d Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Spain
e Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain
f Servicio de Microbiología, Complejo Hospitalario Torrecárdenas, Almería, Spain
g Servicio de Microbiología, Hospital Regional Universitario, Málaga, Spain
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=> "Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Microbiología, Complejo Hospitalario Torrecárdenas, Almería, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Microbiología, Hospital Regional Universitario, Málaga, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación de 3 métodos comerciales de determinación de sensibilidad de ceftolozano/tazobactam frente a <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> resistente a las carbapenemas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2582 "Ancho" => 1683 "Tamanyo" => 180298 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Correlation between ceftolozane/tazobactam MICs as determined by Etest (a); Liofilchem® MIC Test Strips (b); and the Sensititre™ EUROGNCOL panel (c) using microdilution as reference. The number of strains with MICs corresponding to broth microdilution and 1-log<span class="elsevierStyleInf">2</span> dilution are indicated in the dark and light grey squares, respectively. EUCAST breakpoints are presented as solid grey lines.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Ceftolozane/tazobactam was recently introduced as a new drug with excellent activity against <span class="elsevierStyleItalic">Pseudomonas</span><span class="elsevierStyleItalic">aeruginosa</span><a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> because it is stable against overproduction of the intrinsic cephalosporinase AmpC.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> This combination was recently included in some commercial panels, such as the Vitek 2 XN12 card (BioMérieux)<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> and the Microscan NMDR1 panel (Beckman Coulter)<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> for routine antimicrobial susceptibility testing. Validation of other panel types is unknown. Gradient strips for <span class="elsevierStyleItalic">in vitro</span> diagnostic use are also available. When Etest strips were first evaluated with <span class="elsevierStyleItalic">P. aeruginosa</span> isolates, a significant rate of discrepancies between Etest and the reference method was observed.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> The same was true for LiofilmChem gradient strips, where good agreement between microdilution and strips was observed at low concentrations, but with differing results at high concentrations.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> Subsequent analyses have found better correlations for the Etest, but not for LiofilmChem strips, although the number of resistant isolates was not very high<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> and below the 50% recommended by the FDA for assessment of commercial devices.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Carbapenemase-producing <span class="elsevierStyleItalic">P. aeruginosa</span> isolates are resistant to ceftolozane/tazobactam<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> and the inclusion of resistance to ceftolozane/tazobactam has been recommended, along with ceftazidime and cefepime resistance, to increase specificity of detection for carbapenemase producers among carbapenem-resistant <span class="elsevierStyleItalic">P. aeruginosa</span> isolates.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> The aim of the study was to evaluate two gradient strips and a Sensititre panel used to assess the activity of this drug against carbapenem-resistant <span class="elsevierStyleItalic">P. aeruginosa</span> isolates from our region, including a higher number of ceftolozane/tazobactam-resistant isolates than in previous comparisons.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">A total of 100 carbapenem-resistant <span class="elsevierStyleItalic">P. aeruginosa</span> isolates from 11 hospitals in Andalusia were included in the study, which formed part of the SEIMC Carba project<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a>: 41 were metallo-beta-lactamase-producing (21 IMP-producing; 20 VIM-producing isolates) and 59 non-carbapenemase-producing isolates. The isolates were selected to cover a wide range of ceftolozane/tazobactam MIC values. Eighteen (30%) carbapenem-resistant and non-carbapenemase-producing isolates were considered multidrug-resistant strains (MDR) based on additional resistance to two other conventional antipseudomonal beta-lactam groups (antipseudomonal cephalosporins, piperacillin/tazobactam or aztreonam). Susceptibility to ceftolozane/tazobactam was tested by agar diffusion with two types of commercial gradient strips (BioMérieux and LiofilChem) on Mueller Hinton agar, and by commercial microdilution (Sensititre, EURGNCOL panel; 0.25/4–8/4<span class="elsevierStyleHsp" style=""></span>mg/L ceftolozane/tazobactam; Thermo Fisher Scientific); these results were then compared to broth microdilution, following EUCAST recommendations, as the reference method.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> The MIC results by gradient strip were rounded to the next double dilution step for comparison with microdilution; in the case of the EURGNCOL panel, isolates with MIC<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>8 and ≤0.5<span class="elsevierStyleHsp" style=""></span>mg/L were grouped together for the comparison, due to the range of concentrations. For reference microdilution tests, fresh panels were prepared with a range of ceftolozane concentrations from 0.12 to 128<span class="elsevierStyleHsp" style=""></span>mg/L (provided by MERCK SHARP and DOHME) and a fixed concentration of 4<span class="elsevierStyleHsp" style=""></span>mg/L tazobactam. Each isolate was tested in parallel by the four methods described above, on the same day, from a single fresh overnight culture on sheep blood agar. The same bacterial suspension adjusted to 0.5 McFarland in 0.9% NaCl solution was used for microdilution, gradient strip diffusion and the Sensititre panel. Quality controls using <span class="elsevierStyleItalic">P. aeruginosa</span> strain ATCC 27853 were included in each series of experiments.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Essential agreement (EA) was considered when the same MIC values (±1 dilution) were obtained for both methods, using EUCAST as the reference. Bias was calculated for each commercial test as the difference between the percentage of results above and below the reference value, according to the recommendations of ISO 20776-2.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a> The kappa index was used to evaluate concordance using Landis and Koch guidelines.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a> McNemar's test with the Yates correction was used to compare percentages. ISO 20776-2 criteria, acceptable EA rate of ≥90% and interval bias from −30% to 30%, were used to evaluate the performance of the three commercial methods.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0020" class="elsevierStylePara elsevierViewall">Fifty-eight (58%) of the isolates were susceptible to ceftolozane/tazobactam using the reference method. All carbapenemase-producing isolates (66% of isolates had MIC<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>128<span class="elsevierStyleHsp" style=""></span>mg/L) and only one non-carbapenemase-producing isolate (MIC values of 32/4) were resistant to this antibiotic. The MIC<span class="elsevierStyleInf">50</span>, MIC<span class="elsevierStyleInf">90</span>, and MIC range of ceftolozane/tazobactam, as determined by the reference method, were 0.25, 1, and 0.12–6<span class="elsevierStyleHsp" style=""></span>mg/L, respectively, for non-carbapenemase-producing isolates, and 64, 128, and 32–256<span class="elsevierStyleHsp" style=""></span>mg/L respectively, for the carbapenemase producers. The EA rate was below the threshold of acceptance in all cases, the highest being with the EURGNCOL panel and the lowest with Liofilmchem (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.005). Bias was outside the range of acceptance in all three methods due to MIC values being higher than the reference MIC (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), especially in susceptible non-carbapenemase-producing isolates (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The kappa index was below 0.2 with the LiofilChem strips, indicating poor agreement, and in the 0.21–0.40 range for the BioMérieux strips and panels, indicating fair agreement, but this index was good for panels among non-carbapenemase-producing isolates because of aggregated data (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Changes in clinical categories were observed in 3 isolates: 1 carbapenemase-producing isolate was resistant by the reference method and susceptible by the three commercial methods, and 2 non-carbapenemase-producing isolates were both susceptible by the reference method, but 1 was resistant using the Liofilchem strip and EURGNCOL panel, and 1 was resistant only with the EURGNCOL panel.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">In the present study, all three products yielded a higher EA for ceftolozane/tazobactam MICs in <span class="elsevierStyleItalic">P. aeruginosa</span> isolates. Ever since commercial methods for ceftolozane/tazobactam susceptibility testing in <span class="elsevierStyleItalic">P. aeruginosa</span> have been evaluated, the performance of gradient strips has been subject to debate because of the limited number of resistant isolates studied. Our evaluation is the first to include a sufficiently large number of carbapenemase-producing and resistant isolates (42%). In the study involving the largest number of isolates (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>308) to date, carried out by Humphries et al.,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> only 28% of isolates were resistant to ceftolozane/tazobactam. The EA found in our study is lower than that found in other studies using both LiofilmChem strips<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">6,15</span></a> and BioMérieux strips<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> for <span class="elsevierStyleItalic">P. aeruginosa</span>. Our study obtained higher MIC values for the strips and the Sensititre panel than for broth microdilution. Humphries et al. observed lower MIC values for the LiofilmChem strip, but not for the Etest.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> Changes in clinical categories for the two gradient strips were lower than in previous evaluations, which reported very major errors between 2.5%<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> and 25%.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A limitation of our study is that it included only one isolate with MIC values close to the susceptibility cut-off point. Isolates with intermediate ceftolozane/tazobactam MIC values are rare, since more than 40 mutations are required in non-carbapenemase-producing isolates to raise the MIC value for this antibiotic, which normally only occurs in hypermutator strains.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> The strengths of this study are firstly, that it includes broth microdilution as a reference method, secondly, a large number of isolates were evaluated, including a good proportion of resistant ones, and finally, the multicentre origin of the isolates.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In summary, the three commercial systems correctly categorised ceftolozane/tazobactam susceptibility among carbapenem-resistant <span class="elsevierStyleItalic">P. aeruginosa</span> isolates. Both ceftolozane/tazobactam susceptibility testing options for MDR <span class="elsevierStyleItalic">P. aeruginosa</span>, either gradient diffusion or commercial panel, are more accessible than broth microdilution, but our study showed that additional testing with the reference method is recommended when accurate MIC values are needed.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">This study has been funded by Instituto de Salud Carlos III, Spanish Network for Research in Infectious Diseases (RD16/0016/0001)-co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014-2020.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres2039820" "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" => "xpalclavsec1744070" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2039821" "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" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1744069" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-05-27" "fechaAceptado" => "2022-09-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1744070" "palabras" => array:5 [ 0 => "Ceftolozane/tazobactam" 1 => "<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>" 2 => "Metallo-beta-lactamase" 3 => "Gradient strip" 4 => "Sensititre" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1744069" "palabras" => array:5 [ 0 => "Ceftolozano/tazobactam" 1 => "<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>" 2 => "Metalobetalactamasa" 3 => "Tira de gradiente" 4 => "Sensititre®" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "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">Ceftolozane/tazobactam has shown excellent activity against <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, but this drug is not always included in commercial panels. The aim of the study was to evaluate the performance of 2 gradient strips (BioMérieux and Liofilchem) and a commercial microdilution panel (Sensititre, EURGNCOL panel) using this combination against carbapenem-resistant <span class="elsevierStyleItalic">P. aeruginosa</span> isolates.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Three commercial methods were tested with 41 metallo-beta-lactamase-producing and 59 non-carbapenemase-producing <span class="elsevierStyleItalic">P. aeruginosa</span> isolates. Broth microdilution was used as reference.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All carbapenemase-producing isolates and only one non-producing isolate were resistant to this antibiotic. Both essential agreement and bias were outside the acceptance intervals since MIC values were higher than reference values for all three methods. The Kappa index indicated poor or weak agreement. Changes in clinical categories were observed in 3 isolates.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The three methods yielded poor agreement with the reference. Despite the differences in MIC values, fewer than 3% involved category changes.</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">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La combinación ceftolozano/tazobactam ha mostrado una actividad excelente frente a <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, pero este fármaco no siempre se incluye en los paneles comerciales. El objetivo de este estudio es evaluar el rendimiento de 2 tiras de gradiente (BioMérieux® y Liofilchem®) y un panel de microdilución comercial (Sensititre®, panel EURGNCOL) utilizando esta combinación frente a aislados de <span class="elsevierStyleItalic">P. aeruginosa</span> resistente a los carbapenémicos.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se probaron 3 métodos comerciales con 41 aislados productores de metalobetalactamasas y 59 aislados no productores de carbapenemasas de <span class="elsevierStyleItalic">P. aeruginosa</span>. La microdilución de caldo se utilizó como referencia.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Todos los aislados productores de carbapenemasas y solo un aislado no productor fueron resistentes a este antibiótico. Tanto la concordancia esencial como el sesgo se encontraron fuera de los intervalos de aceptación, dado que los valores CMI eran superiores que los valores de referencia para los 3 métodos. El índice de Kappa indicó una concordancia pobre o débil. Se observaron cambios en las categorías clínicas en 3 aislados.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los 3 métodos presentaron una baja concordancia con la microdilución de referencia. A pesar de las diferencias en los valores MIC, menos del 3% implicaron cambios de categoría.</p></span>" "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" ] ] ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2582 "Ancho" => 1683 "Tamanyo" => 180298 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Correlation between ceftolozane/tazobactam MICs as determined by Etest (a); Liofilchem® MIC Test Strips (b); and the Sensititre™ EUROGNCOL panel (c) using microdilution as reference. The number of strains with MICs corresponding to broth microdilution and 1-log<span class="elsevierStyleInf">2</span> dilution are indicated in the dark and light grey squares, respectively. EUCAST breakpoints are presented as solid grey lines.</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">EA: essential agreement.</p>" "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"> \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="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">All carbapenem resistant isolates</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-carbapenemase-producing isolates</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" 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">EA (%) \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">Bias (%) \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">Kappa Index \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">EA (%) \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">Bias (%) \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">Kappa Index \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">E Test strips \t\t\t\t\t\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">80.0 \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">79.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.216 \t\t\t\t\t\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">69.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81.1 \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">0.142 \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">Liofilmchem strips \t\t\t\t\t\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">69.0 \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">87.3 \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">0.179 \t\t\t\t\t\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">50.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.9 \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">0.017 \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">EURGNCOL panel \t\t\t\t\t\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">83.0 \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">75.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.214<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.9 \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">75.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.861<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3382572.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">For calculating the Kappa index, the reference MIC values were grouped as >8 and ≤0.5<span class="elsevierStyleHsp" style=""></span>mg/L, based on the MICs provided by the panel.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Comparison of <span class="elsevierStyleItalic">in vitro</span> performance of gradient tests and the Sensititre EURGNCOL panel <span class="elsevierStyleItalic">versus</span> the broth microdilution method for the determination of susceptibility of <span class="elsevierStyleItalic">P. aeruginosa</span> isolates to ceftolozane/tazobactam.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0085" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ceftolozane/tazobactam for the treatment of serious <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> infections: a multicentre nationwide clinical experience" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Bassetti" 1 => "N. Castaldo" 2 => "A. Cattelan" 3 => "C. Mussini" 4 => "E. Righi" 5 => "C. Tascini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijantimicag.2018.11.001" "Revista" => array:5 [ "tituloSerie" => "Int J Antimicrob Agents" "fecha" => "2019" "volumen" => "53" "paginaInicial" => "408" "paginaFinal" => "415" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0090" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> ceftolozane-tazobactam resistance development requires multiple mutations leading to overexpression and structural modification of <span class="elsevierStyleItalic">ampc</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Cabot" 1 => "S. Bruchmann" 2 => "X. Mulet" 3 => "L. Zamorano" 4 => "B. Moyá" 5 => "C. 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