Brief report
Trend and seasonality of community-acquired Escherichia coli antimicrobial resistance and its dynamic relationship with antimicrobial use assessed by ARIMA models
Tendencia y estacionalidad de las resistencias de Escherichia coli comunitarios y su relación dinámica con el consumo de antimicrobianos mediante modelos ARIMA
María Ángeles Asencio Egeaa,
, María Huertas Vaqueroa, Rafael Carranza Gonzáleza, Óscar Herráez Carrerab, Olga Redondo Gonzálezc, Ángel Arias Ariasc
Corresponding author
a Laboratorio de Microbiología, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
b Unidad de Calidad del Laboratorio, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
c Unidad de Apoyo a la Investigación, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
Read
2127
Timeswas read the article
533
Total PDF
1594
Total HTML
Share statistics
array:24 [ "pii" => "S2529993X18301588" "issn" => "2529993X" "doi" => "10.1016/j.eimce.2018.06.005" "estado" => "S300" "fechaPublicacion" => "2018-10-01" "aid" => "1765" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica" "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Enferm Infecc Microbiol Clin. 2018;36:502-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 323 "formatos" => array:2 [ "HTML" => 243 "PDF" => 80 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0213005X17303075" "issn" => "0213005X" "doi" => "10.1016/j.eimc.2017.10.013" "estado" => "S300" "fechaPublicacion" => "2018-10-01" "aid" => "1765" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Enferm Infecc Microbiol Clin. 2018;36:502-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1064 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 816 "PDF" => 246 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original breve</span>" "titulo" => "Tendencia y estacionalidad de las resistencias de <span class="elsevierStyleItalic">Escherichia coli</span> comunitarios y su relación dinámica con el consumo de antimicrobianos mediante modelos ARIMA" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "502" "paginaFinal" => "506" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Trend and seasonality of community-acquired <span class="elsevierStyleItalic">Escherichia coli</span> antimicrobial resistance and its dynamic relationship with antimicrobial use assessed by ARIMA models" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2539 "Ancho" => 1671 "Tamanyo" => 353600 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estacionalidad del consumo promedio mensual de los antibióticos estudiados (2008-2012). Los antibióticos de la gráfica de arriba son los más utilizados en primaria: fosfomicina, nitrofurantoína, amoxicilina-ácido clavulánico, ciprofloxacino y cotrimoxazol, y muestran una estacionalidad más homogénea que los de la gráfica de abajo: cefuroxima, gentamicina y tobramicina.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María Ángeles Asencio Egea, María Huertas Vaquero, Rafael Carranza González, Óscar Herráez Carrera, Olga Redondo González, Ángel Arias Arias" "autores" => array:6 [ 0 => array:2 [ "nombre" => "María Ángeles" "apellidos" => "Asencio Egea" ] 1 => array:2 [ "nombre" => "María" "apellidos" => "Huertas Vaquero" ] 2 => array:2 [ "nombre" => "Rafael" "apellidos" => "Carranza González" ] 3 => array:2 [ "nombre" => "Óscar" "apellidos" => "Herráez Carrera" ] 4 => array:2 [ "nombre" => "Olga" "apellidos" => "Redondo González" ] 5 => array:2 [ "nombre" => "Ángel" "apellidos" => "Arias Arias" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2529993X18301588" "doi" => "10.1016/j.eimce.2018.06.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529993X18301588?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X17303075?idApp=UINPBA00004N" "url" => "/0213005X/0000003600000008/v1_201809220817/S0213005X17303075/v1_201809220817/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2529993X1830159X" "issn" => "2529993X" "doi" => "10.1016/j.eimce.2017.10.015" "estado" => "S300" "fechaPublicacion" => "2018-10-01" "aid" => "1770" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Enferm Infecc Microbiol Clin. 2018;36:507-16" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2181 "formatos" => array:2 [ "HTML" => 1942 "PDF" => 239 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Continuing medical education: Mycobacterial infections</span>" "titulo" => "Treatment of pulmonary and extrapulmonary tuberculosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "507" "paginaFinal" => "516" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento de la enfermedad tuberculosa pulmonar y extrapulmonar" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Francisco Pascual-Pareja, Raquel Carrillo-Gómez, Victor Hontañón-Antoñana, Mónica Martínez-Prieto" "autores" => array:4 [ 0 => array:2 [ "nombre" => "José Francisco" "apellidos" => "Pascual-Pareja" ] 1 => array:2 [ "nombre" => "Raquel" "apellidos" => "Carrillo-Gómez" ] 2 => array:2 [ "nombre" => "Victor" "apellidos" => "Hontañón-Antoñana" ] 3 => array:2 [ "nombre" => "Mónica" "apellidos" => "Martínez-Prieto" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213005X17303129" "doi" => "10.1016/j.eimc.2017.10.018" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X17303129?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529993X1830159X?idApp=UINPBA00004N" "url" => "/2529993X/0000003600000008/v1_201809220812/S2529993X1830159X/v1_201809220812/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2529993X18301564" "issn" => "2529993X" "doi" => "10.1016/j.eimce.2017.09.008" "estado" => "S300" "fechaPublicacion" => "2018-10-01" "aid" => "1752" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Enferm Infecc Microbiol Clin. 2018;36:498-501" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 282 "formatos" => array:2 [ "HTML" => 187 "PDF" => 95 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Brief report</span>" "titulo" => "Clinical features and outcomes of bacteraemia due to OXA-48-like carbapenemase-producing <span class="elsevierStyleItalic">Klebsiella pneumoniae</span> in a tertiary hospital" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "498" "paginaFinal" => "501" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Características y evolución clínica de las bacteriemias por <span class="elsevierStyleItalic">Klebsiella pneumoniae</span> productora de carbapenemasa tipo OXA-48 en un hospital de tercer nivel" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Madueño, Jonathan González-García, María del Mar Alonso Socas, María Antonia Miguel Gómez, María Lecuona" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Ana" "apellidos" => "Madueño" ] 1 => array:2 [ "nombre" => "Jonathan" "apellidos" => "González-García" ] 2 => array:2 [ "nombre" => "María del Mar" "apellidos" => "Alonso Socas" ] 3 => array:2 [ "nombre" => "María Antonia" "apellidos" => "Miguel Gómez" ] 4 => array:2 [ "nombre" => "María" "apellidos" => "Lecuona" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213005X1730294X" "doi" => "10.1016/j.eimc.2017.09.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X1730294X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529993X18301564?idApp=UINPBA00004N" "url" => "/2529993X/0000003600000008/v1_201809220812/S2529993X18301564/v1_201809220812/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Brief report</span>" "titulo" => "Trend and seasonality of community-acquired <span class="elsevierStyleItalic">Escherichia coli</span> antimicrobial resistance and its dynamic relationship with antimicrobial use assessed by ARIMA models" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "502" "paginaFinal" => "506" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María Ángeles Asencio Egea, María Huertas Vaquero, Rafael Carranza González, Óscar Herráez Carrera, Olga Redondo González, Ángel Arias Arias" "autores" => array:6 [ 0 => array:4 [ "nombre" => "María Ángeles" "apellidos" => "Asencio Egea" "email" => array:1 [ 0 => "marian_asencio@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "María" "apellidos" => "Huertas Vaquero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Rafael" "apellidos" => "Carranza González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Óscar" "apellidos" => "Herráez Carrera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Olga" "apellidos" => "Redondo González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Ángel" "apellidos" => "Arias Arias" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Laboratorio de Microbiología, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Calidad del Laboratorio, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Apoyo a la Investigación, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tendencia y estacionalidad de las resistencias de <span class="elsevierStyleItalic">Escherichia coli</span> comunitarios y su relación dinámica con el consumo de antimicrobianos mediante modelos ARIMA" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2539 "Ancho" => 1671 "Tamanyo" => 354317 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Seasonal variations in average monthly use of the antibiotics studied (2008–2012). The antibiotics in the above graph are those that are most commonly used in primary care (fosfomycin, nitrofurantoin, amoxicillin–clavulanic acid, ciprofloxacin and co-trimoxazole). They show more uniform seasonal variations than those in the below graph (cefuroxime, gentamicin and tobramycin).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The increase in infections due to multidrug-resistant microorganisms, which is generating so much alarm due to their high morbidity and mortality as well as their high healthcare costs,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> has often been linked to the high selective pressure of the antimicrobials used in human health.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">So-called <span class="elsevierStyleItalic">autoregressive integrated moving average</span> (ARIMA) models are statistical tools for finding patterns to enable future estimates to be made. They have been applied to the management of nosocomial infection<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> and more recently to the design of an efficient antimicrobial management programme following an outbreak of carbapenemase-producing bacteria.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> They also enable the relationships between the use of antibiotics and the development of resistance to be measured and estimate the delay to the development of increased resistance to an antibiotic following increased use of that antibiotic.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The objectives of this study are to examine trends and seasonal variations in the resistance of community-acquired <span class="elsevierStyleItalic">Escherichia coli</span> isolates to certain antimicrobials and to measure the dynamic relationship between prior use of antibiotics and the development of resistance for a 5-year period using ARIMA models.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a retrospective study of time series of strains of <span class="elsevierStyleItalic">E. coli</span> isolated from patients from primary care (PC) in a healthcare area with 211,533 inhabitants, use of antibiotics and development of resistance between 2008 and 2012.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The antibiotic use data refer to the population studied and are expressed in terms of defined daily dose (DDD per 1000 inhabitants per day). They were provided by the Dirección General de Farmacia [Directorate General for Pharmacy] of the Autonomous Community. The study of susceptibility to ampicillin (AM), amoxicillin–clavulanic acid (AMC), cefoxitin (CFX), cefotaxime (CFT), cefuroxime (CFM), ciprofloxacin (CIP), co-trimoxazole (SXT), fosfomycin (F), nitrofurantoin (NF), gentamicin (G) and tobramycin (TO) was performed using the VITEK-2® system (bioMérieux, France) in the microbiology laboratory at the reference hospital. The data are expressed in terms of percentage of resistance (number of antibiotic-resistant <span class="elsevierStyleItalic">E. coli</span> isolates divided by total number of isolates). The month was used as a time aggregate both for use and for resistance.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Trends and seasonal variations in resistance were studied using a Poisson regression model where the percentage of resistance was used as a dependent variable. Trends were estimated using the variable representing the number of months elapsed in 5 years. Seasonal variations were estimated using the variable representing the month of the year, taking the month of January as a reference point. The result obtained was interpreted in terms of an incidence rate ratio (IRR) and its 95% confidence interval (95% CI). For trends, the IRR indicates the relative change in the series for each year elapsed. For seasonal variations, the IRR indicates the relative change in each month compared to the month taken as a reference point.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Different ARIMA models were built from time series according to the methodology reported by Box et al. in 1976<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> and adapted by López-Lozano et al. in 2000.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> First, graphs of cross-correlations were used to identify the delays in which the association between use and resistance was most significant. Next, transfer models were built to quantify the relationship between, on the one hand, the use of AMC, CIP, SXT and F and, on the other hand, the development of resistance in <span class="elsevierStyleItalic">E. coli</span> isolates.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 9326 community-acquired <span class="elsevierStyleItalic">E. coli</span> isolates were studied. The average change in the percentage of resistance and the average change in the use of antibiotics are shown in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>, respectively. We found that the use of fosfomycin, co-trimoxazole and nitrofurantoin gradually increased, whereas the use of ciprofloxacin remained stable throughout the period studied. An ascending trend was observed in resistance to the cephalosporins studied, with an average increase in resistance of 7%, 9% and 17% for CFM, CFT and CFX, respectively. Average resistance to aminoglycosides (AMGs) also increased significantly: 11% for G and 25% for TO, as well as 11% for NF. There were two peak increases in AMC resistance, one in 2009 (IRR: 1.25; 95% CI: 1.06–1.47; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.008) and the other in 2011 (IRR: 3.55; 95% CI: 1.14–1.58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). CIP resistance increased as of 2010 (IRR: 1.22; 95% CI: 1.06–1.40; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.006).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding seasonal variations, resistance to AMC and CIP increased significantly in autumn and winter—CIP in December (IRR: 1.27; 95% CI: 1.03–1.57; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.025) and AMC in September (IRR: 1.30; 95% CI: 1.01–1.68; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.039), October (IRR: 1.41; 95% CI: 1.10–1.81; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.007) and December (IRR: 2.19; 95% CI: 1.03–1.70; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.029).</p><p id="par0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a> shows the ARIMA models for AMC, CIP, SXT and F. A positive relationship is seen between the prescription of these antimicrobials and the development of resistance in community-acquired <span class="elsevierStyleItalic">E. coli</span>, with a delay ranging from 2 to 12 months. This relationship was significant for AMC, SXT and F. <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows seasonal variations in average use.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">Our study has once again shown the solid relationship between the use of antimicrobials and the development of resistance for a microorganism as prevalent as <span class="elsevierStyleItalic">E. coli</span>. Analysis of time series enables prediction of the future behaviour of the series studied based on past behaviour. On this basis we sought to predict the development of resistance in community-acquired <span class="elsevierStyleItalic">E. coli</span> isolates based on series of resistance and use of CIP, AMC, SXT and F obtained in the past five years, as well as to estimate the delay in its presentation.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The ascending trend in the resistance of <span class="elsevierStyleItalic">E. coli</span> to cephalosporins, NF and AMG found in our study is consistent with European Antimicrobial Resistance Surveillance System report data.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> This could be related to the dissemination of broad-spectrum beta-lactamases in the community, growing since the 1980s,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> and often presenting co-resistance to other antibiotics such as fluoroquinolones and AMGs. Another possible cause is acquisition of cephalosporins in <span class="elsevierStyleItalic">E. coli</span> from animals.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Peak increases in AMC resistance could be related to greater seasonal use of this and other antibiotics due to the influenza A epidemic which started in Spain in April 2009, leading to higher rates of morbidity and superinfection.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Several studies have used ARIMA models to determine the relationship between the use of antibiotics and the development of resistance.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6,7,12,13</span></a> Hsueh et al. found a significant relationship between increased resistance of <span class="elsevierStyleItalic">E. coli</span> to CFT and CIP and increased use of beta-lactam antibiotics, carbapenems, FQs and AMGs.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> A French study has shown a significant association between the use of fluoroquinolones and increased resistance to ofloxacin and CIP in <span class="elsevierStyleItalic">E. coli</span> strains of urinary origin in hospitalised patients, with delays of less than six months.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> According to our study, each increase by one unit in the use of SXT, F, and AMC is expected to result in an increase in resistance with delays of seven, 10 and 12 months, respectively. We believe that widespread awareness of these data could guide physicians in empirical antibiotic prescription.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Our mean extrahospital antibiotic use in terms of DDD (23.93) was higher than the Spanish mean (20.30) and even higher than the European mean (21.16) in the same period.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> As antimicrobial use is far less managed in a community setting than in a specialised setting, using these predictive models in our setting would offer the option of active intervention to reduce the consequences of this deficiency in reasonable prescription of antibiotics and come closer to the target of the Optimisation Programmes for antibiotics in PC. The implementation of these programmes is a high priority in most Spanish communities.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> Therefore, it would be a good idea to conduct multi-centre studies evaluating the validity of the association and the delays found, as well as to broaden the study to other combinations of microorganisms and antimicrobials.</p><p id="par0075" class="elsevierStylePara elsevierViewall">This study suffers from the limitations particular to retrospective studies: it has a higher risk of information and selection biases. Another limitation is its lack of application of DDDs to the child population.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In conclusion, we found a positive relationship between the use of the antimicrobials analysed and the development of resistance in community-acquired <span class="elsevierStyleItalic">E. coli</span>. This relationship was significant for AMC, SXT and F. The delay in the development of these forms of resistance ranged from seven to 12 months. Thus ARIMA models would enable forecasts to be established to make more reasonable use of antibiotics in a community setting.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1083502" "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" => "xpalclavsec1028174" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1083503" "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" => "xpalclavsec1028175" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:2 [ "identificador" => "xack367607" "titulo" => "Acknowledgement" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-07-14" "fechaAceptado" => "2017-10-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1028174" "palabras" => array:6 [ 0 => "Trend" 1 => "Seasonality" 2 => "Antimicrobial resistance" 3 => "<span class="elsevierStyleItalic">Escherichia coli</span>" 4 => "Antimicrobial use" 5 => "Primary healthcare" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1028175" "palabras" => array:6 [ 0 => "Tendencia" 1 => "Estacionalidad" 2 => "Resistencias" 3 => "<span class="elsevierStyleItalic">Escherichia coli</span>" 4 => "Consumo de antibióticos" 5 => "Atención primaria" ] ] ] ] "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">We studied the trend and seasonality of community-acquired <span class="elsevierStyleItalic">Escherichia coli</span> resistance and quantified its correlation with the previous use of certain antibiotics.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A time series study of resistant community-acquired <span class="elsevierStyleItalic">E. coli</span> isolates and their association with antibiotic use was conducted in a Primary Health Care Area from 2008 to 2012. A Poisson regression model was constructed to estimate the trend and seasonality of <span class="elsevierStyleItalic">E. coli</span> resistance.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A significant increasing trend in mean <span class="elsevierStyleItalic">E. coli</span> resistance to cephalosporins, aminoglycosides and nitrofurantoin was observed. Seasonal resistance to ciprofloxacin and amoxicillin-clavulanic acid was significantly higher in autumn-winter. There was a delay of 7, 10 and 12 months between the use of cotrimoxazole (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.038), fosfomycin (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.024) and amoxicillin-clavulanic acid (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.015), respectively, and the occurrence of <span class="elsevierStyleItalic">E. coli</span> resistance.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">An average delay of 10 months between the previous use of amoxicillin-clavulanic acid, cotrimoxazole and fosfomycin and the appearance of resistant community-acquired <span class="elsevierStyleItalic">E. coli</span> strains was detected.</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">Estudiamos la tendencia y estacionalidad de las resistencias en <span class="elsevierStyleItalic">Escherichia coli</span> comunitario y se cuantifica su asociación con el uso previo de determinados antibióticos.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio de series temporales de las resistencias de aislados comunitarios de <span class="elsevierStyleItalic">E. coli</span> y su relación con el consumo de antibióticos en un área de primaria durante 2008–2012. La tendencia y estacionalidad de las resistencias se estudiaron mediante regresión de Poisson.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se observó un aumento significativo de la resistencia promedio de <span class="elsevierStyleItalic">E. coli</span> a cefalosporinas, nitrofurantoína y aminoglucósidos. La estacionalidad de las resistencias fue significativa en otoño-invierno para amoxicilina-ácido clavulánico y ciprofloxacino. Observamos un retardo de 7, 10 y 12 meses entre el consumo de cotrimoxazol (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,038), fosfomicina (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,024) y amoxicilina-ácido clavulánico (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,015), respectivamente, y la aparición de resistencias.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Detectamos un retardo medio de 10 meses entre la utilización de amoxicilina-ácido clavulánico, cotrimoxazol y fosfomicina, y la aparición de cepas resistentes de <span class="elsevierStyleItalic">E. coli</span> comunitarios.</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" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Asencio Egea MÁ, Huertas Vaquero M, Carranza González R, Herráez Carrera Ó, Redondo González O, Arias Arias Á. Tendencia y estacionalidad de las resistencias de <span class="elsevierStyleItalic">Escherichia coli</span> comunitarios y su relación dinámica con el consumo de antimicrobianos mediante modelos ARIMA. Enferm Infecc Microbiol Clin. 2018;36:502–506.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3660 "Ancho" => 2842 "Tamanyo" => 368249 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">ARIMA models and cross-correlation functions. Relationship between use of amoxicillin-clavulanic acid, ciprofloxacin, co-trimoxazole and fosfomycin and development of resistance in <span class="elsevierStyleItalic">E. coli</span> to these antibiotics.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2539 "Ancho" => 1671 "Tamanyo" => 354317 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Seasonal variations in average monthly use of the antibiotics studied (2008–2012). The antibiotics in the above graph are those that are most commonly used in primary care (fosfomycin, nitrofurantoin, amoxicillin–clavulanic acid, ciprofloxacin and co-trimoxazole). They show more uniform seasonal variations than those in the below graph (cefuroxime, gentamicin and tobramycin).</p>" ] ] 2 => 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:2 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Incident rate \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Amoxicillin–clavulanic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.97–1.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ampicillin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.98–1.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cefoxitin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.17<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="table-entry " align="char" valign="top">1.10–1.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cefotaxime \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.09<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="table-entry " align="char" valign="top">1.02–1.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cefuroxime \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.07<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="table-entry " align="char" valign="top">1.02–1.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ciprofloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.00–1.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Co-trimoxazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.98–1.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fosfomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.96–1.15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gentamicin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.11<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="table-entry " align="char" valign="top">1.05–1.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nitrofurantoin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.11<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="table-entry " align="char" valign="top">1.04–1.18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tobramycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.25<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="table-entry " align="char" valign="top">1.18–1.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1850188.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Significant increase in average resistance (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Average change in percentage of resistance (2008–2012).</p>" ] ] 3 => 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="spar0065" class="elsevierStyleSimplePara elsevierViewall">Overall DDD: total DDD for therapeutic group J01 (antibacterials for systemic use) at the health centres in our setting by year of study.</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="table-head " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">DDD: Annual incident rate</th><th class="td" title="table-head " align="left" valign="top" scope="col">Incident rate 2008–2012 \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Antibiotic \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2008 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2009 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2010 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2011 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2012 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Average change (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ampicillin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.95 (0.79–1.11) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Amoxicillin–clavulanic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.01 (0.98–1.05) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cefuroxime \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 (0.75–0.97)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ciprofloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.01 (0.97–1.05) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Co-trimoxazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.10 (1.02–1.18)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fosfomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.25 (1.06–1.44)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nitrofurantoin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.18 (0.92–1.45) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gentamicin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.19 (0.92–1.46) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tobramycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.01 (0.79–1.24) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Overall DDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1850189.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Significant change in average use of antibiotics (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Average change in antibiotic consumption (2008–2012).</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" => "Clinical and economic impact of bacteremia with extended-spectrum β-lactamase-producing <span class="elsevierStyleItalic">Enterobacteriaceae</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.J. Schwaber" 1 => "S. Navon-Venezia" 2 => "K.S. Kaye" 3 => "R. Ben-Ami" 4 => "D. Schwartz" 5 => "Y. Carmeli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.50.4.1257-1262.2006" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2006" "volumen" => "50" "paginaInicial" => "1257" "paginaFinal" => "1262" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16569837" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of antibiotic changes in empirical therapy on antimicrobial resistance in intensive care unit-acquired infections" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Allegranzi" 1 => "R. Luzzati" 2 => "A. Luzzani" 3 => "F. Girardini" 4 => "L. Antozzi" 5 => "R. Raiteri" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hosp Infect" "fecha" => "2002" "volumen" => "52" "paginaInicial" => "136" "paginaFinal" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12392905" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The impact of antibiotic use on the incidence and resistance pattern of extended-spectrum beta-lactamase-producing bacteria in primary and secondary healthcare settings" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Aldeyab" 1 => "S. Harbarth" 2 => "N. Vernaz" 3 => "M.P. Kearney" 4 => "M.G. Scott" 5 => "F.W. Darwish Elhajji" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2125.2011.04161.x" "Revista" => array:6 [ "tituloSerie" => "Br J Clin Pharmacol" "fecha" => "2012" "volumen" => "74" "paginaInicial" => "171" "paginaFinal" => "179" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22150975" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modelling the impact of antibiotic use and infection control practices on the incidence of hospital-acquired methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>: a time-series analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Aldeyab" 1 => "D.L. Monnet" 2 => "J.M. Lopez-Lozano" 3 => "C.M. Hughes" 4 => "M.G. Scott" 5 => "M.P. Kearney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jac/dkn198" "Revista" => array:6 [ "tituloSerie" => "J Antimicrob Chemother" "fecha" => "2008" "volumen" => "62" "paginaInicial" => "593" "paginaFinal" => "600" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18467307" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Forecasting carbapenem resistance from antimicrobial consumption surveillance: lessons learnt from an OXA-48-producing <span class="elsevierStyleItalic">Klebsiella pneumoniae</span> outbreak in a West London renal unit" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Gharbi" 1 => "L.S. Moore" 2 => "M. Gilchrist" 3 => "C.P. Thomas" 4 => "K. Bamford" 5 => "E.T. Brannigan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijantimicag.2015.03.005" "Revista" => array:6 [ "tituloSerie" => "Int J Antimicrob Agents" "fecha" => "2015" "volumen" => "46" "paginaInicial" => "150" "paginaFinal" => "156" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25979640" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modelling and forecasting antimicrobial resistance and its dynamic relationship to antimicrobial use: a time series analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. López-Lozano" 1 => "D.L. Monnet" 2 => "A. Yagüe" 3 => "A. Burgos" 4 => "N. Gonzalo" 5 => "P. Campillos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Antimicrob Agents" "fecha" => "2000" "volumen" => "14" "paginaInicial" => "21" "paginaFinal" => "31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10717497" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evolution of fluoroquinolone resistance among <span class="elsevierStyleItalic">Escherichia coli</span> urinary tract isolates from a French university hospital: application of the dynamic regression model" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Mahamat" 1 => "J.P. Lavigne" 2 => "P. Fabbro-Peray" 3 => "J.M. Kinowski" 4 => "J.P. Daures" 5 => "A. Sotto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1469-0691.2005.01098.x" "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Infect" "fecha" => "2005" "volumen" => "11" "paginaInicial" => "301" "paginaFinal" => "306" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15760427" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Time series analysis: forecasting and control" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Box" 1 => "G. Jenkins" 2 => "G. Reinsel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:4 [ "edicion" => "1st ed." "fecha" => "1976" "editorial" => "Holden-Day" "editorialLocalizacion" => "San Francisco, CA" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antimicrobial resistance surveillance in Europe 2012. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net)" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "European Centre for Disease Prevention and Control" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2015" "editorial" => "ECDC" "editorialLocalizacion" => "Stockholm" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extended-spectrum [beta]-lactamase producing <span class="elsevierStyleItalic">Escherichia coli:</span> changing epidemiology and clinical impact" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Oteo" 1 => "M. Pérez-Vázquez" 2 => "J. Campos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Opin Infect Dis" "fecha" => "2010" "volumen" => "23" "paginaInicial" => "320" "paginaFinal" => "326" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20614578" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dissemination of the chromosomally encoded CMY-2 cephalosporinase gene in <span class="elsevierStyleItalic">Escherichia coli</span> isolated from animals" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.X. Fang" 1 => "J. Sun" 2 => "L. Li" 3 => "H. Deng" 4 => "T. Huang" 5 => "Q.E. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijantimicag.2015.04.003" "Revista" => array:6 [ "tituloSerie" => "Int J Antimicrob Agents" "fecha" => "2015" "volumen" => "46" "paginaInicial" => "209" "paginaFinal" => "213" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26048440" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relationships between antimicrobial use and antimicrobial resistance in Gram-negative bacteria causing nosocomial infections from 1991–2003 at a university hospital in Taiwan" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.R. Hsueh" 1 => "W.H. Chen" 2 => "K.T. Luh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijantimicag.2005.08.016" "Revista" => array:6 [ "tituloSerie" => "Int J Antimicrob Agents" "fecha" => "2005" "volumen" => "26" "paginaInicial" => "463" "paginaFinal" => "472" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16280243" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Making sense of antimicrobial use and resistance surveillance data: application of ARIMA and transfer function models" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.L. Monnet" 1 => "J.M. López-Lozano" 2 => "P. Campillos" 3 => "A. Burgos" 4 => "A. Yagüe" 5 => "N. Gonzalo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Infect" "fecha" => "2001" "volumen" => "7" "numero" => "Suppl 5" "paginaInicial" => "S29" "paginaFinal" => "S36" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surveillance of antimicrobial consumption in Europe 2012" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "European Centre for Disease Prevention and Control" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2014" "editorial" => "ECDC" "editorialLocalizacion" => "Stockholm" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Programa integral de prevención, control de las infecciones relacionadas con la asistencia sanitaria, y uso apropiado de los antimicrobianos (PIRASOA). Available from: <a id="intr0010" class="elsevierStyleInterRef" href="http://ws140.juntadeandalucia.es/pirasoa">http://ws140.juntadeandalucia.es/pirasoa</a>" ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack367607" "titulo" => "Acknowledgement" "texto" => "<p id="par0090" class="elsevierStylePara elsevierViewall">We would like to thank Dr José María Tenías Burillo for his unconditional support.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/2529993X/0000003600000008/v1_201809220812/S2529993X18301588/v1_201809220812/en/main.assets" "Apartado" => array:4 [ "identificador" => "66624" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Brief reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/2529993X/0000003600000008/v1_201809220812/S2529993X18301588/v1_201809220812/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529993X18301588?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 9 | 1 | 10 |
| 2024 September | 18 | 4 | 22 |
| 2024 August | 24 | 5 | 29 |
| 2024 July | 14 | 3 | 17 |
| 2024 June | 15 | 5 | 20 |
| 2024 May | 15 | 10 | 25 |
| 2024 April | 13 | 8 | 21 |
| 2024 March | 29 | 3 | 32 |
| 2024 February | 27 | 1 | 28 |
| 2024 January | 31 | 2 | 33 |
| 2023 December | 20 | 3 | 23 |
| 2023 November | 24 | 6 | 30 |
| 2023 October | 43 | 6 | 49 |
| 2023 September | 18 | 0 | 18 |
| 2023 August | 25 | 0 | 25 |
| 2023 July | 11 | 2 | 13 |
| 2023 June | 21 | 1 | 22 |
| 2023 May | 32 | 1 | 33 |
| 2023 April | 57 | 4 | 61 |
| 2023 March | 51 | 3 | 54 |
| 2023 February | 12 | 5 | 17 |
| 2023 January | 62 | 42 | 104 |
| 2022 December | 11 | 3 | 14 |
| 2022 November | 25 | 7 | 32 |
| 2022 October | 20 | 10 | 30 |
| 2022 September | 27 | 15 | 42 |
| 2022 August | 24 | 10 | 34 |
| 2022 July | 18 | 9 | 27 |
| 2022 June | 16 | 6 | 22 |
| 2022 May | 18 | 10 | 28 |
| 2022 April | 41 | 9 | 50 |
| 2022 March | 31 | 8 | 39 |
| 2022 February | 28 | 5 | 33 |
| 2022 January | 27 | 4 | 31 |
| 2021 December | 31 | 7 | 38 |
| 2021 November | 21 | 8 | 29 |
| 2021 October | 24 | 16 | 40 |
| 2021 September | 13 | 7 | 20 |
| 2021 August | 17 | 16 | 33 |
| 2021 July | 18 | 9 | 27 |
| 2021 June | 18 | 6 | 24 |
| 2021 May | 26 | 8 | 34 |
| 2021 April | 52 | 30 | 82 |
| 2021 March | 18 | 11 | 29 |
| 2021 February | 25 | 7 | 32 |
| 2021 January | 17 | 6 | 23 |
| 2020 December | 16 | 9 | 25 |
| 2020 November | 25 | 12 | 37 |
| 2020 October | 17 | 11 | 28 |
| 2020 September | 26 | 14 | 40 |
| 2020 August | 15 | 8 | 23 |
| 2020 July | 13 | 9 | 22 |
| 2020 June | 14 | 11 | 25 |
| 2020 May | 24 | 12 | 36 |
| 2020 April | 16 | 8 | 24 |
| 2020 March | 35 | 12 | 47 |
| 2020 February | 24 | 7 | 31 |
| 2020 January | 24 | 12 | 36 |
| 2019 December | 22 | 7 | 29 |
| 2019 November | 9 | 1 | 10 |
| 2019 October | 23 | 4 | 27 |
| 2019 September | 35 | 10 | 45 |
| 2019 August | 9 | 1 | 10 |
| 2019 July | 11 | 7 | 18 |
| 2019 June | 21 | 16 | 37 |
| 2019 May | 57 | 13 | 70 |
| 2019 April | 17 | 7 | 24 |
| 2018 December | 1 | 0 | 1 |
| 2018 October | 1 | 0 | 1 |
| 2018 September | 2 | 0 | 2 |
Show all
