Macrolide-lincosamide-streptogramin B resistance phenotypes and their associated genotypes in Staphylococcus aureus isolates from a tertiary level public hospital of Uruguay

array:24 ["pii" => "S0325754119301154" "issn" => "03257541" "doi" => "10.1016/j.ram.2019.10.004" "estado" => "S300" "fechaPublicacion" => "2020-07-01" "aid" => "369" "copyright" => "Asociación Argentina de Microbiología" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Argent Microbiol. 2020;52:202-10" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 22 "formatos" => array:3 [ "EPUB" => 5 "HTML" => 7 "PDF" => 10 ] ] "itemSiguiente" => array:19 [ "pii" => "S0325754119301130" "issn" => "03257541" "doi" => "10.1016/j.ram.2019.10.003" "estado" => "S300" "fechaPublicacion" => "2020-07-01" "aid" => "367" "copyright" => "Asociación Argentina de Microbiología" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Argent Microbiol. 2020;52:211-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 27 "formatos" => array:3 [ "EPUB" => 4 "HTML" => 8 "PDF" => 15 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Brief report" "titulo" => "First characterization of K. pneumoniae ST11 clinical isolates harboring blaKPC-3 in Latin America" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "211" "paginaFinal" => "216" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Primera caracterización de aislamientos clínicos de K. pneumoniae ST11 portadores de blaKPC-3 en América Latina" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 829 "Ancho" => 1984 "Tamanyo" => 91029 ] ] "descripcion" => array:1 [ "en" => "K. pneumoniae pulsed-field gel electrophoresis." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Virginia Garcia-Fulgueiras, Yuliana Zapata, Romina Papa-Ezdra, Pablo Ávila, Leticia Caiata, Verónica Seija, Ana E. Rojas Rodriguez, Carmen Magallanes, Carolina Márquez Villalba, Rafael Vignoli" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Virginia" "apellidos" => "Garcia-Fulgueiras" ] 1 => array:2 [ "nombre" => "Yuliana" "apellidos" => "Zapata" ] 2 => array:2 [ "nombre" => "Romina" "apellidos" => "Papa-Ezdra" ] 3 => array:2 [ "nombre" => "Pablo" "apellidos" => "Ávila" ] 4 => array:2 [ "nombre" => "Leticia" "apellidos" => "Caiata" ] 5 => array:2 [ "nombre" => "Verónica" "apellidos" => "Seija" ] 6 => array:2 [ "nombre" => "Ana E." "apellidos" => "Rojas Rodriguez" ] 7 => array:2 [ "nombre" => "Carmen" "apellidos" => "Magallanes" ] 8 => array:2 [ "nombre" => "Carolina" "apellidos" => "Márquez Villalba" ] 9 => array:2 [ "nombre" => "Rafael" "apellidos" => "Vignoli" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0325754119301130?idApp=UINPBA00004N" "url" => "/03257541/0000005200000003/v1_202010070634/S0325754119301130/v1_202010070634/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S032575411930094X" "issn" => "03257541" "doi" => "10.1016/j.ram.2019.10.002" "estado" => "S300" "fechaPublicacion" => "2020-07-01" "aid" => "365" "copyright" => "Asociación Argentina de Microbiología" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Argent Microbiol. 2020;52:198-201" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 19 "formatos" => array:3 [ "EPUB" => 3 "HTML" => 9 "PDF" => 7 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "INFORME BREVE" "titulo" => "Primer aislamiento de Leptospira borgpetersenii serovar Hardjo tipo Hardjo Bovis a partir de un caso clínico en Argentina" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "198" "paginaFinal" => "201" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "First isolation of Leptospira borgpetersenii serovar Hardjo type Hardjo Bovis from a clinical case in cattle in Argentina" ] ] "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" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 969 "Ancho" => 1250 "Tamanyo" => 63580 ] ] "descripcion" => array:1 [ "es" => "Amplificaciones obtenidas mediante PCR específica para el serovar Hardjo Bovis. Los productos de amplificación fueron separados en gel de agarosa al 2%. CM: CienMarker (marcador de PM); 1: serovar Pomona; 2: serovar Castellon; 3: serovar Canicola; 4: cepa aislada; 5: control+." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ariel Alejandro Koval, Bibiana Felicitas Brihuega, Sylvia Grune Loffler, S. López, Marcos Saint Martin, Gustavo Germán Lagioia, Juan Ramón Insaugarat" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Ariel Alejandro" "apellidos" => "Koval" ] 1 => array:2 [ "nombre" => "Bibiana Felicitas" "apellidos" => "Brihuega" ] 2 => array:2 [ "nombre" => "Sylvia" "apellidos" => "Grune Loffler" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "López" ] 4 => array:2 [ "nombre" => "Marcos" "apellidos" => "Saint Martin" ] 5 => array:2 [ "nombre" => "Gustavo Germán" "apellidos" => "Lagioia" ] 6 => array:2 [ "nombre" => "Juan Ramón" "apellidos" => "Insaugarat" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S032575411930094X?idApp=UINPBA00004N" "url" => "/03257541/0000005200000003/v1_202010070634/S032575411930094X/v1_202010070634/es/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Macrolide-lincosamide-streptogramin B resistance phenotypes and their associated genotypes in Staphylococcus aureus isolates from a tertiary level public hospital of Uruguay" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "202" "paginaFinal" => "210" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Lorena Pardo, Virginia Machado, Dianna Cuello, Paula Aguerrebere, Verónica Seija, Valeria Braga, Gustavo Varela" "autores" => array:7 [ 0 => array:3 [ "nombre" => "Lorena" "apellidos" => "Pardo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Virginia" "apellidos" => "Machado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Dianna" "apellidos" => "Cuello" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Paula" "apellidos" => "Aguerrebere" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Verónica" "apellidos" => "Seija" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Valeria" "apellidos" => "Braga" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:4 [ "nombre" => "Gustavo" "apellidos" => "Varela" "email" => array:2 [ 0 => "gvarela@higiene.edu.uy" 1 => "gvarela1961@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Bacteriology and Virology Department, Medicine School, Universidad de la República, Montevideo Alfredo Navarro 3051 (south entrance), 11800, Uruguay" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Bacteriology Laboratory, “Hospital Pasteur”, Montevideo, Larravide 2458, 11800, Uruguay" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Laboratory of Public Health, Alfredo Navarro 3051 (north-entrance), Montevideo, Uruguay" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fenotipos de resistencia a macrólidos lincosamidas-estreptograminas B y sus genotipos asociados en Staphylococcus aureus aislados en un hospital público de nivel terciario en Uruguay" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2842 "Ancho" => 3010 "Tamanyo" => 619818 ] ] "descripcion" => array:1 [ "en" => "Pulsed-field gel electrophoresis (PFGE) dendrogram of methicillin-resistant S. aureus isolates showing PTs, PGs, associated profile of resistance, SCCmec type and sample source. Dashed line indicates PGs (named as A, B and C, with ≥80% similarity and more than 2 isolates in each). cMLSB, constitutive resistance to macrolide, lincosamide and type B streptogramin; iMLSB, inducible resistance to macrolide, lincosamide and type B streptogramin; MSB, resistance to macrolide and streptogramin B; L, resistance to lincosamides; CIP, resistance to ciprofloxacin; GM, resistance to gentamicin; RIF, resistance to rifampicin; SXT, resistance to trimethoprim-sulfamethoxazole; None, susceptible to all tested antibiotics." ] ] ] "textoCompleto" => "IntroductionStaphylococcus aureus is a versatile microorganism that is found in the human microbiota and is also responsible for both hospital- or community-acquired illnesses. The diseases that it causes range from mild lesions that compromise skin and soft tissues to more severe conditions such as pneumonia, septic arthritis, endocarditis, osteomyelitis, and sepsis<a class="elsevierStyleCrossRefs" href="#bib0255">12,31,33</a>. A biological characteristic of S. aureus is its ability to acquire exogenous genetic material that encodes several resistance mechanisms for different antibiotics. The mobile staphylococcal chromosomal cassette mec (SCCmec) that carries the mecA gene which encodes PBP2a, which is responsible for methicillin-resistance (MRSA), was likely acquired by horizontal transfer from a related species<a class="elsevierStyleCrossRef" href="#bib0235">8</a>. Three categories of MRSA are currently recognized, healthcare-associated (HA-MRSA), community-associated (CA-MRSA) and livestock-associated MRSA (LA-MRSA) according to epidemiological criteria, site of infection acquisition (community, hospital or animal contact), associated antibiotic susceptibility profile and genotype, including SCC element type<a class="elsevierStyleCrossRefs" href="#bib0250">11,34,35</a>. S. aureus belonging to the three aforementioned categories have been implicated around the world in both sporadic cases and outbreaks of human staphylococcal diseases<a class="elsevierStyleCrossRefs" href="#bib0215">4,16,37</a>. Macrolides, lincosamides, and type B streptogramin (MLSB) antibiotics can be alternatives for treatment of MRSA infections<a class="elsevierStyleCrossRef" href="#bib0375">36</a>. However, the increase in macrolide, lincosamide and type B streptogramin resistant isolates complicates the empirical antimicrobial treatment selection in S. aureus infections<a class="elsevierStyleCrossRef" href="#bib0265">14</a>. A fairly common resistance mechanism observed in S. aureus is due to the action of efflux pumps, encoded by the mrsA and mrsB genes responsible for pumping macrolide and streptogramin B antibiotics out of the bacteria (MSB resistance phenotype). On the other hand, the exclusive resistance to lincosamides (L resistance phenotype) mediated by lincomycin nucleotidyl-transferase enzymes and codified by genes lnuA-F, is occasionally observed. Isolates that carry lnu genes resist high levels of lincomycin but can be susceptible to clindamycin in the disk induction test<a class="elsevierStyleCrossRefs" href="#bib0285">18,23</a>. In S. aureus and other gram-positive bacteria, resistance to MLSB antibiotics is mainly due to the 23S rRNA modification by adenine-N methyltransferase enzymes. This modification compromises macrolide, lincosamide and type B streptogramin activity. Genes encoding these methylases have been designated as erm genes and their expression can be constitutive (cMLSB resistance phenotype) or inducible (iMLSB resistance phenotype)<a class="elsevierStyleCrossRef" href="#bib0260">13</a>. Isolates with the iMLSB phenotype show in vitro resistance to erythromycin, but can falsely seem to be susceptible to clindamycin. These isolates have a high rate of spontaneous mutation to constitutive resistance phenotypes that can be selected by the usage of clindamycin, resulting in therapeutic failure. This fact highlights the importance of performing a correct laboratory identification using any of the recommended tests<a class="elsevierStyleCrossRefs" href="#bib0210">3,6</a>. In our region, data about the prevalence of resistance to MLSB antibiotics in isolates of S. aureus recovered from adult individuals are scarce. This study aimed to investigate the presence of the different erythromycin and clindamycin resistance phenotypic profiles and also to determine the responsible genotypes in a set of S. aureus isolates recovered in a public, tertiary level hospital of Montevideo city, Uruguay.Materials and methodsWe study 100 consecutive, non-duplicate S. aureus isolates obtained from patients admitted at the “Hospital Pasteur” (HP) from July 2012 to December2013. Setting The HP is a 250-bed tertiary level public and teaching hospital for all medical and surgical specialties. Patients receiving medical care at the HP are adults (>16 years of age) and often come from low-income households.Bacterial isolates, source, identification and antimicrobial susceptibility testing.S. aureus isolates were identified using the automated system VITEK 2 version 7.01 and classified as methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) according to the obtained MIC value to oxacillin and the result of the cefoxitin test. The site of infection was taken from the laboratory records. Erythromycin (ERY) and clindamycin (CLI) phenotypes were assessed and interpreted using the D-zone test published by Steward et al.<a class="elsevierStyleCrossRef" href="#bib0355">32</a> (D phenotype: D-shaped clear zone around the CLI disk near the ERY disk; D+ phenotype: like the previous one but with small colonies growing close to the CLI disk in an otherwise clear zone; HD phenotype: two zones of growth around the CLI disk: one zone is a light growth extending from the CLI disk to the second zone, where the growth is much thicker; R phenotype: growth to the edge of both CLI and ERY disks; MSB phenotype: a clear zone around the CLI disk; L phenotype: growth only up to the CLI disk; S phenotype: susceptible to both the CLI and ERY disks)<a class="elsevierStyleCrossRefs" href="#bib0210">3,2</a>.The IHSA 23 strain of S. aureus was used as a positive control for the D-test. Minimum inhibitory concentration (MIC) to erythromycin, clindamycin, vancomycin, teicoplanin and oxacillin was determined by the agar dilution method according to the Clinical and Laboratory Standards Institute recommendations<a class="elsevierStyleCrossRef" href="#bib0225">6</a>. The susceptibility patterns to ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole, tetracycline and rifampicin were taken from the VITEK report. Broth macrodilution assays (BMA) that included combinations of CLI plus ERY were conducted with minor modifications in accordance with the general procedure previously described by Steward et al.<a class="elsevierStyleCrossRef" href="#bib0355">32</a>. Briefly, the combinations were tested using CLI at final concentrations ranging from 0.5 to 8μg/ml plus ERY at final concentrations ranging from 0.03 to 0.12μg/ml. Reading was done after 18–24h of incubation at 35–37°C. This procedure was applied to those isolates that showed the iMLSB, cMLSB, MSB and S phenotypes by disk diffusion tests. S. aureus ATCC 29213 (CLI and ERY-susceptible) was included as control. The isolates were stored at −20°C in skimmed milk for further studies.Molecular typing and antibiotic resistance gene detection. Bacterial DNA was obtained from isolated colonies using the Wizard genomic DNA preparation kit (Promega. Madison, Wis, USA) adding 20mg/ml lysostaphin (Sigma Chemical) in the cell lysis step. Detection of the mecA gene and SCCmec typing was performed in all MRSA isolates by a multiplex PCR assay previously described by Oliveira DC and H. de Lencastre<a class="elsevierStyleCrossRef" href="#bib0295">20</a>. MRSA isolates that carried the SCCmec type IV were arbitrarily taken as community-associated methicillin-resistant S. aureus (CA-MRSA) while those that carried the SCCmec type I, II, or III were grouped as health-care associated methicillin-resistant S. aureus (HA-MRSA). PCR detection of the ermA, ermB, ermC, msrA and msrB genes was performed on all isolates that showed the following resistance phenotypes: iMLSB (D and D+); cMLSB (HD and R); and MSB using standard protocols and previously described primers<a class="elsevierStyleCrossRef" href="#bib0270">15</a>. S. aureus MM122-35 was used as positive control for the ermA gene, S. aureus MM2 was used as a positive control for the ermB gene, and S. aureus MM523 for the ermC gene. S. aureus MM3627 was included as positive control for both msr A and B genes. All the strains were kindly provided by Genoveva Pensado (Bacteriology and Virology department). Ultrapure RNAse/DNAse free water was used as negative control in all PCR reactions.Pulsed field gel electrophoresis (PFGE). DNA macro-restriction with the SmaI enzyme and further separation of fragments by pulsed field gel electrophoresis (PFGE) were carried out using a previously described protocol<a class="elsevierStyleCrossRef" href="#bib0315">24</a>. The obtained profiles were analyzed by the unweighted pair group method with arithmetic average (UPGMA) using BioNumerics v.7.1. The isolates that showed ≥80% similarity were included into the same pulsogroup (PG), while those that showed ≥95% similarity were considered to be of identical pulsotype (PT)<a class="elsevierStyleCrossRef" href="#bib0240">9</a>. S. aureus subsp. aureus (strain NCTC 8325) was included as reference size marker.ResultsSource of analyzed S. aureus isolates and resistance phenotypesWe studied 100 isolates of S. aureus. Twenty-three of them were recovered from invasive diseases including bacteremia (n=10; 43.4%), ventilator-associated pneumonia (n=8; 35%), deep abscesses (n=4; 17.3%) and acute meningoencephalitis (n=1; 4.3%). On the other hand, 77 isolates were recovered from skin and soft tissue infections (SSTIs) including superficial abscesses (n=39; 50%), wounds (n=22; 28.5%), cellulitis (n=11; 14.2%) and whitlows (n=5; 6.4%).Fifty-three isolates were classified as MSSA and the remaining 47 as MRSA (all of them carried the mecA gene); 25 corresponded to CA-MRSA and 22 to HA-MRSA, according to the above described abbreviated criterion. The distribution of the SCCmec types in HA-MRSA was as follows: SCCmec type I, 5 isolates; SCCmec type II, 15 isolates and SCCmec type III, 2 isolates. Fifteen percent of the MSSA isolates were resistant to MLSB antibiotics, whereas this figure increased to 63.8% in the MRSA (CA-MRSA and HA-MRSA) isolates. All S. aureus isolates included in this study were susceptible to vancomycin and teicoplanin. Four isolates (4%) were resistant to rifampicin, all of them carrying the SCCmec type II. Twenty two out of 47 (46.8%) MRSA showed resistance to ciprofloxacin (HA-MRSA, n=21; CA-MRSA, n=1). However, only 4 out of 53 (7.5%) MSSA were resistant to this antibiotic. Eight S. aureus isolates (8%) showed resistance to gentamicin, 4 (7.5%) corresponded to MSSA isolates and 4 (8.5%) to MRSA (HA-MRSA, n=3; CA-MRSA, n=1). One methicillin-susceptible isolate was resistant to tetracycline. The only S. aureus isolate that showed resistance to trimethoprim-sulfamethoxazole belonged to the HA-MRSA group. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the resistant phenotypes to MLSB antibiotics found in MRSA and MSSA isolates. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the percentage of resistance to macrolides and lincosamides found in MRSA (HA-MRSA, CA-MRSA) and MSSA isolates. Three out of the 10 isolates with iMLSB resistance showed the D+ phenotype in the disk-diffusion test. The isolates with the iMLSB resistance phenotype (n=10; 5 CA-MRSA and 5 MSSA) showed MICs for CLI ≤0.125μg/ml and those with phenotype S (n=62; MSSA 45 and CA-MRSA 17) had MICs for CLI ≤0.25μg/ml. In those isolates that exhibited the cMLSB resistance phenotype (n=22; HA-MRSA, 21 and MSSA, 1 isolate) MICs for CLI were ≥256μg/ml. As shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, the combination of 2μg/ml of CLI plus 0.12μg/ml of ERY in the BM assay allowed us to differentiate between isolates displaying iMLSB or cMLSB resistance phenotypes and those with the MSB or S phenotype. Seven out of 10 isolates that showed the iMLSB resistant phenotype (D, 4 isolates and D+, 3 isolates) grew in the presence of CLY at 8μg/ml plus ERY 0.12μg/ml and all the isolates (n=22) that showed the cMLSB resistance phenotype (HD and R) grew in the presence of the combination 8μg/ml of CLI plus ERY 0.12μg/ml.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Distribution of the resistance genes to MLSB antibiotics among S. aureus isolatesAs shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>, all the isolates that showed the iMLSB resistance phenotype in the D-test carried the combination of the ermA and ermC genes. Instead, in those isolates that displayed the cMLSB resistance phenotype (HD or R) the predominant genotype was ermA (alone or in combination with other resistance genes). In those isolates that showed the cMLSB (HD) phenotype, the combination of the ermA and mrs genes was seen more frequently (6 out of 8) than in those that displayed the cMLSB (R) phenotype (2 in 14) (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). The ermB gene was found in just one isolate with the cMLSB resistance phenotype. The responsible genotype was not studied in the CA-MRSA isolate that showed the L resistance phenotype.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>SmaI-PFGE profiles in MRSA and MSSA isolates. As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>, the SmaI-PFGE profile analysis of MRSA isolates revealed a wide variety of PTs (n=41) and 3 clusters (pulsogroups, PG: A, B and C, with ≥80% similarity and more than 2 isolates in each). Cluster A included 6 isolates, one with SCCmec IV, one with SCCmec III, one with SCCmec I and finally 3 isolates that carried the SCCmec II element with the cMLSB resistance phenotype that showed 100% identity and were recovered from 3 inpatients located in the same surgery ward. The only isolate with the L resistance phenotype recovered in this study was located in this PG. Cluster B (9 isolates) included 8 CA-MRSA isolates. Three of them (including an isolate carrying the SCCmec type II) showed 100% similarity and were visually identical to the main pulsotype found in local CA-MRSA isolates recovered in Uruguay between 2001 and 2002 (PFGE profile A1, type USA1100). Other 3 isolates in this PG showed 100% similarity among them (including the single CA-MRSA isolate with the cMLSB resistance phenotype recovered in this study) and were also visually similar to the CA-MRSA PFGE profile A1. Cluster C also included CA-MRSA isolates. The 5 CA-MRSA isolates that displayed the iMLSB resistance phenotype belonged to 5 different PTs (see <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In the MSSA isolates, 52 PTs and 3 PGs (A, B and C, ≥80% similarity, more than 2 isolates in each) (see <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) were recognized. Only 2 isolates showed 95% similarity and were located in the PG C. This PG included 7 isolates, 2 of them with the iMLSB phenotype (see <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>DiscussionClindamycin has been used for the treatment of severe staphylococcal diseases, taking into account some of its pharmacological properties. However, resistance can develop in isolates with the iMLSB phenotype, and spontaneous constitutively resistant mutants have arisen from such isolates during clindamycin therapy, determining therapeutic failures in some patients<a class="elsevierStyleCrossRef" href="#bib0245">10</a>. This is the first local report about the distribution of resistance phenotypes to MLSB antibiotics and their responsible genes in a set of S. aureus isolates recovered from adult inpatients in a public hospital. The overall prevalence of resistance to MLSB antibiotics was 38%. This figure is similar to that reported by Abbas et al.<a class="elsevierStyleCrossRef" href="#bib0200">1</a> (40%) in a study conducted in India that included 500 isolates of S. aureus recovered in a tertiary hospital and otherwise higher than that also found in India by Prabhu et al. (28.42%)<a class="elsevierStyleCrossRef" href="#bib0320">25</a>. Similarly to what happened in Serbia and India, in the current study most S. aureus isolates (62%) showed susceptibility to both macrolide and lincosamide antibiotics. However, the distribution of the resistance phenotypes was different from that reported by those authors. In Serbia, iMLSB was the most frequent resistance phenotype detected (31.5–33.7%); instead in India it was MSB (17%) followed by both cMLSB and iMLSB resistance phenotypes (11.6% and 10.8%, respectively)<a class="elsevierStyleCrossRefs" href="#bib0300">21,25</a>. In this study the overall data show that the predominant resistance phenotype was cMLSB (22%) followed by iMLSB (10%), MSB (5%) and L (1%). Similar figures were reported by Sedaghat in the Iranian teaching hospital and also by Paz Pereira et al. in neighboring Brazil<a class="elsevierStyleCrossRefs" href="#bib0210">3,28</a>. The cMLSB resistance phenotype prevailed among HA-MRSA isolates (SCCmec I, II and III) (20/22; 91%), which is in concordance with similar studies carried out in other countries<a class="elsevierStyleCrossRefs" href="#bib0205">2,5,29,39</a>. In this work the prevalence of the iMLSB resistance phenotype was similar among MRSA (CA-MRSA and HA-MRSA) (5/47; 10.6%) and MSSA (5/53; 9%) isolates. This result is not in concordance with the findings reported by Abbas et al.<a class="elsevierStyleCrossRef" href="#bib0200">1</a> or Rahbar et al.<a class="elsevierStyleCrossRef" href="#bib0325">26</a>, which showed a higher prevalence of the iMLSB resistance phenotype in MSSA isolates. Furthermore, in contrast to the findings of Mišic et al.<a class="elsevierStyleCrossRef" href="#bib0300">21</a> in Serbia, none of the HA-MRSA (SCCmec I, II and III) isolates studied here showed the iMLSB resistance phenotype (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The prevalence of MSSA isolates with the iMLSB resistance phenotype found in our study (9%) was lower than that reported by Shoji et al. in Japan (25.4%)<a class="elsevierStyleCrossRef" href="#bib0345">30</a>. As we will comment below, the results obtained by SmaI-PFGE showed great genetic diversity in both MSSA and MRSA isolates with iMLSB and cMLSB resistance phenotypes (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). This suggests a broad diffusion of the responsible resistance genes rather than the circulation of a predominant PT. The overall prevalence of the MSB resistance phenotype was 5%; this figure being lower than that reported by Mišic et al.<a class="elsevierStyleCrossRef" href="#bib0300">21</a> in Serbia (17.6%) but similar to the results (6%) obtained by Sedaghat et al.<a class="elsevierStyleCrossRef" href="#bib0335">28</a> in the Iranian teaching hospitals<a class="elsevierStyleCrossRefs" href="#bib0300">21,28</a>. The combination of msrA and msrB genes was detected in all (5) isolates that showed this resistance phenotype. Only one isolate showed the L resistance phenotype; as formerly seen in Argentina, which corresponded to a CA-MRSA isolate carrying SCCmec type IV<a class="elsevierStyleCrossRef" href="#bib0285">18</a>. The occurrence of this resistance type remains low at the HP hospital (1%) as was described previously<a class="elsevierStyleCrossRefs" href="#bib0280">17,21,23</a>. The prevalence of resistance phenotypes to MLSB antibiotics vary depending on the analyzed country, geographic area and even the type of patient (inpatients vs. outpatients; hospital vs. community origin; children vs. adults; public vs. private institutions; patients or healthcare workers included, among others). This global trend highlights the need for each country, region or hospital to use its own bacterial resistance surveillance program<a class="elsevierStyleCrossRefs" href="#bib0205">2,5,26,29</a>. The obtained results in the BM assay combining 2μg/ml of CLI plus 0.12μg/ml of ERY allowed us to differentiate between isolates displaying iMLSB or cMLSB phenotypes and those with the MSB or the S phenotype. However, in contrast with Steward et al.’s findings<a class="elsevierStyleCrossRef" href="#bib0355">32</a>, in this study some S. aureus isolates with an iMLSB resistance phenotype and positive D test were able to grow at higher concentrations of clindamycin. This could be partly explained by the fact that these isolates with the D or D+ phenotype carry the combination of erm and msr genes, as we discussed further<a class="elsevierStyleCrossRef" href="#bib0355">32</a>. All analyzed S. aureus isolates (n=100) were susceptible to vancomycin and teicoplanin. However, it is necessary to conduct an active surveillance to early detect the presence of glycopeptide-resistant strains. As expected, most of the S. aureus isolates grouped in this study as HA-MRSA (21 of 22) showed ciprofloxacin resistance. Only 4 of 100 isolates were resistant to rifampicin and all of them corresponded to HA-MRSA.Resistance genes to MLSB antibiotics and genetic comparison by SmaI-PFGEThe PCR analysis identified the ermA gene as the most frequent MLSB resistance gene followed by ermC. The ermA gene was detected individually or in combination with other genes such as ermC, msrA and msrB in 30 (79%) out of 38 S. aureus resistant to MLSB antibiotics. In 12 of them, especially in HA-MRSA (11/14), it was individually detected and all these isolates showed a cMLSB resistance phenotype (R) (see <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). This result is in concordance with previous findings obtained in European hospitals<a class="elsevierStyleCrossRef" href="#bib0330">27</a>. In general, the ermA genes are mainly detected in MRSA isolates and are located in transposons related to Tn554, while the ermC genes are frequently responsible for resistance in MSSA and are located in plasmids. Based on the SmaI PFGE results, we can rule out the hypothesis of a broad hospital spread of a single pulsotype with a cMLSB resistance phenotype carrying the ermA gene. Only three isolates belonging to cluster A (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) showed 100% similarity; they carried the SCCmec type II and were recovered from three patients of the same ward. This probably corresponded to a case of limited intrahospital cross contamination. In the two above cited studies, there are no data about the genetic comparison of the included strains; therefore, it cannot be ruled out that they pertained to prevalent clones. In similar studies conducted in Brazil and European countries the ermC gene predominated over the ermA gene<a class="elsevierStyleCrossRefs" href="#bib0290">19,22,37</a>. As it occurred in Brazil, we merely detected one resistant isolate that carried the ermB gene and showed the cMLSB resistance phenotype<a class="elsevierStyleCrossRef" href="#bib0230">7</a>. This low prevalence (2.6%) was expected, taking into account that we only included isolates collected from adult patients. This gene is frequently found in S. aureus isolates from animal origin and also in pediatric CA-MRSA isolates<a class="elsevierStyleCrossRefs" href="#bib0230">7,38</a>. The PCR analysis identified the msrA and msrB genes, alone or combined, in 16 isolates belonging to the MSSA, CA-MRSA or HA-MRSA categories with iMLSB, cMLSB and MSB resistance phenotypes. An interesting result of this study was the high rate of combination of MLSB resistance genes. The most commonly detected profile was ermA plus ermC (n=14), followed by the combination of ermA plus msrA (n=7), many of which also bore the msrB gene. All isolates with the iMLSB resistance phenotype (n=10) carried both ermA and ermC genes, and three of them also harbored the msrB gene (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). The SmaI-PFGE results showed great genetic diversity in both MSSA and MRSA isolates with iMLSB and cMLSB resistance phenotypes. They support the wide spread of the resistance genes to MLSB antibiotics in these studied clinical S. aureus isolates rather than the circulation of a predominant PT. This study has two limitations: MRSA isolates were considered to be CA-MRSA or HA-MRSA only according to the SCCmec type that they carried and the use of PCR for erm genes does not allow to differentiate between isolates with iMLSB or cMLSB resistance phenotypes.ConclusionsThe overall prevalence of resistance to MLSB antibiotics in this group of clinical S. aureus isolates was 38% and the resistance phenotype distribution was as follows: cMLSB, 22%; iMLSB, 10%; MSB, 5% and L, 1%. In these resistant isolates we detected, ermA, ermC, ermB and mrsA/B genes. The single ermA gene was commonly found in HA-MRSA (SCCmec I, II and III) isolates, mainly in those with a cMLSB R resistance phenotype; whereas the combination ermA and ermC was more commonly observed in MSSA or CA-MRSA (SCCmec IV) isolates with inducible resistance expression (iMLSB phenotype). There was a high rate of combination of MLSB resistance genes and the obtained patterns by SmaI-PFGE suggest a great genetic diversity in this group of MRSA and MSSA MLSB resistant isolates. The obtained results demonstrate the local presence of S. aureus resistant to MLSB antibiotics and its most frequently described responsible genes. These isolates (especially those with the inducible resistance phenotype, iMLSB) may be associated with therapeutic failures; therefore, efforts should be directed toward their correct detection using appropriate laboratory tests, particularly among those recovered from hospitalized individuals suffering from comorbidities or receiving immunosuppressive treatment.FundingThis work was supported by a grant of the Comisión Sectorial de Investigación Científica (CSIC), Universidad de la República [program I+D group 290].Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1395067" "titulo" => "Highlights" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1395068" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1278597" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1395069" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0015" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1278596" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 7 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Source of analyzed S. aureus isolates and resistance phenotypes" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Distribution of the resistance genes to MLS antibiotics among S. aureus isolates" ] ] ] 8 => array:3 [ "identificador" => "sec0030" "titulo" => "Discussion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Resistance genes to MLS antibiotics and genetic comparison by SmaI-PFGE" ] ] ] 9 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack485163" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-07-16" "fechaAceptado" => "2019-10-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1278597" "palabras" => array:7 [ 0 => "Staphylococcus aureus" 1 => "MLSB resistance" 2 => "D-test" 3 => "ermA" 4 => "ermC" 5 => "msrA/B" 6 => "SmaI-PFGE" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1278596" "palabras" => array:7 [ 0 => "Staphylococcus aureus" 1 => "Resistencia a MLSB" 2 => "D-test" 3 => "ermA" 4 => "ermC" 5 => "msrA/B" 6 => "SmaI-PFGE" ] ] ] ] "tieneResumen" => true "highlights" => array:2 [ "titulo" => "Highlights" "resumen" => "<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•The overall prevalence of MLSB resistance in this set of S. aureus was 38%.</li><li class="elsevierStyleListItem" id="lsti0010">•The phenotype distribution was: cMLSB, 22%; iMLSB, 10%; MSB, 5% and L, 1%.</li><li class="elsevierStyleListItem" id="lsti0015">•ermA gene was prevalent in HA-MRSA isolates, mainly in those with a cMLSB phenotype.</li><li class="elsevierStyleListItem" id="lsti0020">•The combination ermA and ermC genes was prevalent in isolates with inducible resistance.</li><li class="elsevierStyleListItem" id="lsti0025">•SmaI-PFGE results suggest a great genetic diversity in this MLSB resistant isolates.</li></ul>" ] "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "This study was undertaken to investigate the resistance phenotypes to macrolide-lincosamide-streptogramin B (MLSB) antibiotics and their associated genotypes in isolates of Staphylococcus aureus. We analyzed one hundred, consecutive, non-duplicate isolates (methicillin-susceptible MSSA, n=53 and methicillin-resistant MRSA, n=47) obtained from various clinical samples between July 2012 to December 2013. The resistance profile to MLSB antibiotics was determined by phenotypic methods and the resistance genes were detected by PCR assays. All of the isolates were subjected to pulsed-field gel electrophoresis (SmaI-PFGE). The overall prevalence of resistance to MLSB antibiotics was 38% and the resistance phenotype distribution was as follows: cMLSB, 22%; iMLSB, 10%; MSB, 5% and L, 1%. We detected ermA, ermC, ermB and mrsA/B genes in these resistant isolates. The single ermA gene was commonly observed mainly in those with a cMLSB R phenotype, whereas the combination ermA and ermC was more commonly observed in isolates with inducible expression. The patterns of SmaI-PFGE suggest a great genetic diversity in both MRSA and MSSA resistant to MLSB antibiotics. The results demonstrate the local presence of S. aureus resistant to MLSB antibiotics and its most frequently described responsible genes. Some of these isolates, especially those with the iMLSB phenotype, may be associated with therapeutic failure. Therefore, efforts should be directed to the correct detection of all MLSB resistant isolates using appropriate laboratory tests. PFGE results reveal a wide spread of resistance genes rather than the circulation of S. aureus clones resistant to MLSB antibiotics." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Los objetivos de este estudio fueron investigar en Staphylococcus aureus la presencia de fenotipos resistentes a los antibióticos macrólidos, lincosamidas y estreptograminas tipoB (MLSB) y conocer sus genotipos responsables. Analizamos 100 aislamientos consecutivos, no duplicados (53 sensibles a meticilina [MSSA] y 47 resistentes a meticilina [MRSA]), obtenidos entre 2012 y 2013 a partir de diferentes muestras clínicas. El perfil de resistencia a los antibióticos MLSB fue determinado por métodos fenotípicos y los genes de resistencia se detectaron por PCR. Todos los aislamientos fueron comparados por SmaI-PFGE. La prevalencia global de resistencia a los antibióticos MLSB fue del 38% y la distribución de los fenotipos de resistencia fue la siguiente: cMLSB, 22%; iMLSB, 10%; MSB, 5%; L, 1%. Se detectaron los genes ermA, ermC y mrsA/B en los aislamientos resistentes. El gen ermA se observó, sobre todo, en aislamientos con fenotipo resistente constitutivoR (cMLSB), mientras que la combinación ermA y ermC se detectó principalmente en aislamientos con resistencia inducible (iMLSB). Los patrones de SmaI-PFGE sugieren una gran diversidad genética en los aislamientos resistentes a los antibióticos MLSB, tanto MRSA como MSSA. Los resultados demuestran la presencia local de S. aureus resistentes a los antibióticos MLSB y de sus genes responsables más frecuentemente descritos. Estos cultivos, especialmente aquellos con fenotipo resistente iMLSB, pueden asociarse con fallas terapéuticas. Por lo tanto, los esfuerzos deben dirigirse a la correcta detección de todos los cultivos resistentes a MLSB utilizando pruebas de laboratorio adecuadas. Los resultados de SmaI-PFGE sugieren una amplia diseminación de genes de resistencia, más que la circulación de clones resistentes a los antibióticos MLSB." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2842 "Ancho" => 3010 "Tamanyo" => 619818 ] ] "descripcion" => array:1 [ "en" => "Pulsed-field gel electrophoresis (PFGE) dendrogram of methicillin-resistant S. aureus isolates showing PTs, PGs, associated profile of resistance, SCCmec type and sample source. Dashed line indicates PGs (named as A, B and C, with ≥80% similarity and more than 2 isolates in each). cMLSB, constitutive resistance to macrolide, lincosamide and type B streptogramin; iMLSB, inducible resistance to macrolide, lincosamide and type B streptogramin; MSB, resistance to macrolide and streptogramin B; L, resistance to lincosamides; CIP, resistance to ciprofloxacin; GM, resistance to gentamicin; RIF, resistance to rifampicin; SXT, resistance to trimethoprim-sulfamethoxazole; None, susceptible to all tested antibiotics." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2578 "Ancho" => 3010 "Tamanyo" => 604169 ] ] "descripcion" => array:1 [ "en" => "Pulsed-field gel electrophoresis (PFGE) dendrogram of methicillin-susceptible S. aureus isolates showing PTs, PGs, associated profile of resistance and sample source. Dashed line indicates PGs (named as A, B and C, with ≥80% similarity and more than 2 isolates in each). cMLSB, constitutive resistance to macrolide, lincosamide and type B streptogramin; iMLSB, inducible resistance to macrolide, lincosamide and type B streptogramin; MSB, resistance to macrolide and streptogramin B; L, resistance to lincosamides; CIP, resistance to ciprofloxacin; GM, resistance to gentamicin; RIF, resistance to rifampicin; TET, resistance to tetracycline; None, susceptible to all tested antibiotics." ] ] 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="\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="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MRSA with SCCmec type</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Subtotal \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">MSSA n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Total \t\t\t\t\t\t\n \t\t\t\t\t\t</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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">I n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">II n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">III n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IV n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" 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="" 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="" 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></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">iMLSB<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (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">0 (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">0 (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">5 (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">5 (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">5 (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">10 (10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">cMLSB<a class="elsevierStyleCrossRef" href="#tblfn0010">b</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">4 (4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (14%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (21%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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">22 (22%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MSB<a class="elsevierStyleCrossRef" href="#tblfn0015">c</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">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (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">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (5%) \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">L <a class="elsevierStyleCrossRef" href="#tblfn0020">d</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">0 (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">0 (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">0 (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">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (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">1 (1%) \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">S <a class="elsevierStyleCrossRef" href="#tblfn0025">e</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">0 (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">0 (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">0 (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">17 (17%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (17%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 (45%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 (62%) \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">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (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">15 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (25%) \t\t\t\t\t\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">47 (47%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (53%) \t\t\t\t\t\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">100 (100%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2394234.png" ] ] ] "notaPie" => array:5 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "iMLSB: inducible resistance to MLSB antibiotics." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "cMLSB: constitutive resistance to MLSB antibiotics." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "MSB: resistance to erythromycin." ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "L: resistance only to clindamycin." ] 4 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "e" "nota" => "S: erythromycin and clindamycin susceptible." ] ] ] "descripcion" => array:1 [ "en" => "Distribution of phenotypes to MLSB antibiotics in S. aureus isolates using the D-zone test." ] ] 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:1 [ "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-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">% of resistance to \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MRSA with SCCmec IV (n=25) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MRSA with SCCmec I, II, III (n=22) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MSSA (n=53) \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">Macrolides(iMLSB, cMLSB and MSB resistance phenotypes) \t\t\t\t\t\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">28% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.1% \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">Lincosamides(iMLSB, cMLSB and L resistance phenotypes) \t\t\t\t\t\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">28% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.3% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2394235.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Resistance to MLSB antibiotics in S. aureus isolates." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "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="\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="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disk diffusion phenotype results</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">iMLSB<a class="elsevierStyleCrossRef" href="#tblfn0030">a</a></th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">cMLSB<a class="elsevierStyleCrossRef" href="#tblfn0035">b</a> (HD/R) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">MSB<a class="elsevierStyleCrossRef" href="#tblfn0040">c</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">S<a class="elsevierStyleCrossRef" href="#tblfn0045">d</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">D \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">D+ \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="" 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="" 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="" 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></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">No. of isolates \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (8/14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No. of isolates that grew with</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CLI 8μg/ml plus</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">ERY 0.12μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \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">ERY 0.06μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \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">ERY 0.03μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CLI 4μg/ml plus</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">ERY 0.12μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \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">ERY 0.06μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \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">ERY 0.03μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CLI 2μg/ml plus</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">ERY 0.12μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \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">ERY 0.06μ/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \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">ERY 0.03μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CLI 1μg/ml plus</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">ERY 4μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \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">ERY 1μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CLI 0.5μg/ml plus</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">ERY 1μg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><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 \t\t\t\t\t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\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">MIC100 to CLI without ERY \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤0.125μg/ml</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">≥250μg/ml \t\t\t\t\t\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">≤0.125μg/ml \t\t\t\t\t\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">≤0.250μg/ml \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2394236.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "a" "nota" => "Inducible resistance to MLSB antibiotics, D: clear zone around the CLI disk near to the ERY disk; D+: like the previous one but with small colonies growing up to the CLI disk in an otherwise clear zone." ] 1 => array:3 [ "identificador" => "tblfn0035" "etiqueta" => "b" "nota" => "cMLSB (HD/R) Constitutive resistance to MLSB antibiotics, HD: two zones of growth appear around the CLI disk, one zone is a light growth extending from the CLI disk to the second zone where the growth is much thicker; R: growth to the edge of both the CLI and ERY disks." ] 2 => array:3 [ "identificador" => "tblfn0040" "etiqueta" => "c" "nota" => "MSB clear zone around the CLI disk." ] 3 => array:3 [ "identificador" => "tblfn0045" "etiqueta" => "d" "nota" => "S susceptible to both the CLI and ERY disks." ] ] ] "descripcion" => array:1 [ "en" => "Results of Broth Macrodilution Assays (BMA)." ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "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="\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="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resistance phenotype in the D-test assay</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"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">iMLSB<a class="elsevierStyleCrossRef" href="#tblfn0050">a</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">cMLSB (HD) <a class="elsevierStyleCrossRef" href="#tblfn0055">b</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">cMLSB (R) <a class="elsevierStyleCrossRef" href="#tblfn0060">c</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">MSB<a class="elsevierStyleCrossRef" href="#tblfn0065">d</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">L <a class="elsevierStyleCrossRef" href="#tblfn0070">e</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=10 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=8 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=14 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=5 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="left" valign="middle">Genotype</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermA/10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermA/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermA/11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">msrA/5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-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">ermC/10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermB/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermC/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">msrB/5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND<a class="elsevierStyleCrossRef" href="#tblfn0075">f</a> \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">msrB/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermA+ermC+msrA+msrB/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermA+msrA/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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermA+msrA/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ermA+msrB/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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2394237.png" ] ] ] "notaPie" => array:6 [ 0 => array:3 [ "identificador" => "tblfn0050" "etiqueta" => "a" "nota" => "iMLSB: inducible resistance to MLSB antibiotics." ] 1 => array:3 [ "identificador" => "tblfn0055" "etiqueta" => "b" "nota" => "cMLSB (HD): constitutive resistance to MLSB antibiotics (two zones of growth appear around the CLI disk, one zone is a light growth extending from the CLI disk to the second zone where the growth is much thicker)." ] 2 => array:3 [ "identificador" => "tblfn0060" "etiqueta" => "c" "nota" => "cMLSB (R): constitutive resistance to MLSB antibiotics (growth to the edge of both the CLI and ERY disks)." ] 3 => array:3 [ "identificador" => "tblfn0065" "etiqueta" => "d" "nota" => "MSB: resistance only to erythromycin." ] 4 => array:3 [ "identificador" => "tblfn0070" "etiqueta" => "e" "nota" => "L: growth only up to the CLI disk." ] 5 => array:3 [ "identificador" => "tblfn0075" "etiqueta" => "f" "nota" => "ND, not done, unknown." ] ] ] "descripcion" => array:1 [ "en" => "Genotypes found in isolates of S. aureus resistant to MLSB antibiotics." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0200" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of MLSB resistance and observation of ermA and ermC genes at a tertiary care hospital" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. 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Fenotipos de resistencia a macrólidos lincosamidas-estreptograminas B y sus genotipos asociados en Staphylococcus aureus aislados en un hospital público de nivel terciario en Uruguay

Lorena Pardoa, Virginia Machadoa, Dianna Cuelloa, Paula Aguerreberea, Verónica Seijab,c, Valeria Bragaa, Gustavo Varelaa,

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gvarela@higiene.edu.uy
gvarela1961@gmail.com

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a Bacteriology and Virology Department, Medicine School, Universidad de la República, Montevideo Alfredo Navarro 3051 (south entrance), 11800, Uruguay

b Bacteriology Laboratory, “Hospital Pasteur”, Montevideo, Larravide 2458, 11800, Uruguay

c Laboratory of Public Health, Alfredo Navarro 3051 (north-entrance), Montevideo, Uruguay

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        "titulo" => "Fenotipos de resistencia a macr&#243;lidos lincosamidas-estreptograminas B y sus genotipos asociados en <span class="elsevierStyleItalic">Staphylococcus aureus</span> aislados en un hospital p&#250;blico de nivel terciario en Uruguay"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Pulsed-field gel electrophoresis &#40;PFGE&#41; dendrogram of methicillin-resistant <span class="elsevierStyleItalic">S&#46; aureus</span> isolates showing PTs&#44; PGs&#44; associated profile of resistance&#44; SCC<span class="elsevierStyleItalic">mec</span> type and sample source&#46; Dashed line indicates PGs &#40;named as A&#44; B and C&#44; with &#8805;80&#37; similarity and more than 2 isolates in each&#41;&#46; cMLS<span class="elsevierStyleInf">B</span>&#44; constitutive resistance to macrolide&#44; lincosamide and type B streptogramin&#59; iMLS<span class="elsevierStyleInf">B</span>&#44; inducible resistance to macrolide&#44; lincosamide and type B streptogramin&#59; MS<span class="elsevierStyleInf">B</span>&#44; resistance to macrolide and streptogramin B&#59; L&#44; resistance to lincosamides&#59; CIP&#44; resistance to ciprofloxacin&#59; GM&#44; resistance to gentamicin&#59; RIF&#44; resistance to rifampicin&#59; SXT&#44; resistance to trimethoprim-sulfamethoxazole&#59; None&#44; susceptible to all tested antibiotics&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Staphylococcus aureus</span> is a versatile microorganism that is found in the human microbiota and is also responsible for both hospital- or community-acquired illnesses&#46; The diseases that it causes range from mild lesions that compromise skin and soft tissues to more severe conditions such as pneumonia&#44; septic arthritis&#44; endocarditis&#44; osteomyelitis&#44; and sepsis<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">12&#44;31&#44;33</span></a>&#46; A biological characteristic of <span class="elsevierStyleItalic">S&#46; aureus</span> is its ability to acquire exogenous genetic material that encodes several resistance mechanisms for different antibiotics&#46; The mobile staphylococcal chromosomal cassette <span class="elsevierStyleItalic">mec</span> &#40;SCC<span class="elsevierStyleItalic">mec</span>&#41; that carries the <span class="elsevierStyleItalic">mecA</span> gene which encodes PBP2a&#44; which is responsible for methicillin-resistance &#40;MRSA&#41;&#44; was likely acquired by horizontal transfer from a related species<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a>&#46; Three categories of MRSA are currently recognized&#44; healthcare-associated &#40;HA-MRSA&#41;&#44; community-associated &#40;CA-MRSA&#41; and livestock-associated MRSA &#40;LA-MRSA&#41; according to epidemiological criteria&#44; site of infection acquisition &#40;community&#44; hospital or animal contact&#41;&#44; associated antibiotic susceptibility profile and genotype&#44; including SCC element type<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">11&#44;34&#44;35</span></a>&#46; <span class="elsevierStyleItalic">S&#46; aureus</span> belonging to the three aforementioned categories have been implicated around the world in both sporadic cases and outbreaks of human staphylococcal diseases<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">4&#44;16&#44;37</span></a>&#46; Macrolides&#44; lincosamides&#44; and type B streptogramin &#40;MLS<span class="elsevierStyleInf">B</span>&#41; antibiotics can be alternatives for treatment of MRSA infections<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">36</span></a>&#46; However&#44; the increase in macrolide&#44; lincosamide and type B streptogramin resistant isolates complicates the empirical antimicrobial treatment selection in <span class="elsevierStyleItalic">S&#46; aureus</span> infections<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a>&#46; A fairly common resistance mechanism observed in <span class="elsevierStyleItalic">S&#46; aureus</span> is due to the action of efflux pumps&#44; encoded by the <span class="elsevierStyleItalic">mrsA</span> and <span class="elsevierStyleItalic">mrsB</span> genes responsible for pumping macrolide and streptogramin B antibiotics out of the bacteria &#40;MS<span class="elsevierStyleInf">B</span> resistance phenotype&#41;&#46; On the other hand&#44; the exclusive resistance to lincosamides &#40;L resistance phenotype&#41; mediated by lincomycin nucleotidyl-transferase enzymes and codified by genes <span class="elsevierStyleItalic">lnuA-F</span>&#44; is occasionally observed&#46; Isolates that carry <span class="elsevierStyleItalic">lnu</span> genes resist high levels of lincomycin but can be susceptible to clindamycin in the disk induction test<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">18&#44;23</span></a>&#46; In <span class="elsevierStyleItalic">S&#46; aureus</span> and other gram-positive bacteria&#44; resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics is mainly due to the 23S rRNA modification by adenine-N methyltransferase enzymes&#46; This modification compromises macrolide&#44; lincosamide and type B streptogramin activity&#46; Genes encoding these methylases have been designated as <span class="elsevierStyleItalic">erm</span> genes and their expression can be constitutive &#40;cMLS<span class="elsevierStyleInf">B</span> resistance phenotype&#41; or inducible &#40;iMLS<span class="elsevierStyleInf">B</span> resistance phenotype&#41;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a>&#46; Isolates with the iMLS<span class="elsevierStyleInf">B</span> phenotype show in vitro resistance to erythromycin&#44; but can falsely seem to be susceptible to clindamycin&#46; These isolates have a high rate of spontaneous mutation to constitutive resistance phenotypes that can be selected by the usage of clindamycin&#44; resulting in therapeutic failure&#46; This fact highlights the importance of performing a correct laboratory identification using any of the recommended tests<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#44;6</span></a>&#46; In our region&#44; data about the prevalence of resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics in isolates of <span class="elsevierStyleItalic">S&#46; aureus</span> recovered from adult individuals are scarce&#46; This study aimed to investigate the presence of the different erythromycin and clindamycin resistance phenotypic profiles and also to determine the responsible genotypes in a set of <span class="elsevierStyleItalic">S&#46; aureus</span> isolates recovered in a public&#44; tertiary level hospital of Montevideo city&#44; Uruguay&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Materials and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">We study 100 consecutive&#44; non-duplicate <span class="elsevierStyleItalic">S&#46; aureus</span> isolates obtained from patients admitted at the &#8220;Hospital Pasteur&#8221; &#40;HP&#41; from July 2012 to December2013&#46; <span class="elsevierStyleItalic">Setting</span> The HP is a 250-bed tertiary level public and teaching hospital for all medical and surgical specialties&#46; Patients receiving medical care at the HP are adults &#40;&#62;16 years of age&#41; and often come from low-income households&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Bacterial isolates&#44; source&#44; identification and antimicrobial susceptibility testing</span>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">S&#46; aureus</span> isolates were identified using the automated system VITEK 2 version 7&#46;01 and classified as methicillin-resistant &#40;MRSA&#41; or methicillin-susceptible &#40;MSSA&#41; according to the obtained MIC value to oxacillin and the result of the cefoxitin test&#46; The site of infection was taken from the laboratory records&#46; Erythromycin &#40;ERY&#41; and clindamycin &#40;CLI&#41; phenotypes were assessed and interpreted using the D-zone test published by Steward et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a> &#40;D phenotype&#58; D-shaped clear zone around the CLI disk near the ERY disk&#59; D&#43; phenotype&#58; like the previous one but with small colonies growing close to the CLI disk in an otherwise clear zone&#59; HD phenotype&#58; two zones of growth around the CLI disk&#58; one zone is a light growth extending from the CLI disk to the second zone&#44; where the growth is much thicker&#59; R phenotype&#58; growth to the edge of both CLI and ERY disks&#59; MS<span class="elsevierStyleInf">B</span> phenotype&#58; a clear zone around the CLI disk&#59; L phenotype&#58; growth only up to the CLI disk&#59; S phenotype&#58; susceptible to both the CLI and ERY disks&#41;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#44;2</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The IHSA 23 strain of <span class="elsevierStyleItalic">S&#46; aureus</span> was used as a positive control for the D-test&#46; Minimum inhibitory concentration &#40;MIC&#41; to erythromycin&#44; clindamycin&#44; vancomycin&#44; teicoplanin and oxacillin was determined by the agar dilution method according to the Clinical and Laboratory Standards Institute recommendations<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">6</span></a>&#46; The susceptibility patterns to ciprofloxacin&#44; gentamicin&#44; trimethoprim-sulfamethoxazole&#44; tetracycline and rifampicin were taken from the VITEK report&#46; Broth macrodilution assays &#40;BMA&#41; that included combinations of CLI plus ERY were conducted with minor modifications in accordance with the general procedure previously described by Steward et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a>&#46; Briefly&#44; the combinations were tested using CLI at final concentrations ranging from 0&#46;5 to 8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml plus ERY at final concentrations ranging from 0&#46;03 to 0&#46;12<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#46; Reading was done after 18&#8211;24<span class="elsevierStyleHsp" style=""></span>h of incubation at 35&#8211;37<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; This procedure was applied to those isolates that showed the iMLS<span class="elsevierStyleInf">B</span>&#44; cMLS<span class="elsevierStyleInf">B</span>&#44; MS<span class="elsevierStyleInf">B</span> and S phenotypes by disk diffusion tests&#46; <span class="elsevierStyleItalic">S&#46; aureus</span> ATCC 29213 &#40;CLI and ERY-susceptible&#41; was included as control&#46; The isolates were stored at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C in skimmed milk for further studies&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Molecular typing and antibiotic resistance gene detection&#46;</span> Bacterial DNA was obtained from isolated colonies using the Wizard genomic DNA preparation kit &#40;Promega&#46; Madison&#44; Wis&#44; USA&#41; adding 20<span class="elsevierStyleHsp" style=""></span>mg&#47;ml lysostaphin &#40;Sigma Chemical&#41; in the cell lysis step&#46; Detection of the <span class="elsevierStyleItalic">mecA</span> gene and SCC<span class="elsevierStyleItalic">mec</span> typing was performed in all MRSA isolates by a multiplex PCR assay previously described by Oliveira DC and H&#46; de Lencastre<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">20</span></a>&#46; MRSA isolates that carried the SCC<span class="elsevierStyleItalic">mec</span> type IV were arbitrarily taken as community-associated methicillin-resistant <span class="elsevierStyleItalic">S&#46; aureus</span> &#40;CA-MRSA&#41; while those that carried the SCC<span class="elsevierStyleItalic">mec</span> type I&#44; II&#44; or III were grouped as health-care associated methicillin-resistant <span class="elsevierStyleItalic">S&#46; aureus</span> &#40;HA-MRSA&#41;&#46; PCR detection of the <span class="elsevierStyleItalic">ermA</span>&#44; <span class="elsevierStyleItalic">ermB&#44; ermC</span>&#44; <span class="elsevierStyleItalic">msrA</span> and <span class="elsevierStyleItalic">msrB</span> genes was performed on all isolates that showed the following resistance phenotypes&#58; iMLS<span class="elsevierStyleInf">B</span> &#40;D and D&#43;&#41;&#59; cMLS<span class="elsevierStyleInf">B</span> &#40;HD and R&#41;&#59; and MS<span class="elsevierStyleInf">B</span> using standard protocols and previously described primers<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">15</span></a>&#46; <span class="elsevierStyleItalic">S&#46; aureus</span> MM122-35 was used as positive control for the <span class="elsevierStyleItalic">ermA</span> gene&#44; <span class="elsevierStyleItalic">S&#46; aureus</span> MM2 was used as a positive control for the <span class="elsevierStyleItalic">ermB</span> gene&#44; and <span class="elsevierStyleItalic">S&#46; aureus</span> MM523 for the <span class="elsevierStyleItalic">ermC</span> gene&#46; <span class="elsevierStyleItalic">S&#46; aureus</span> MM3627 was included as positive control for both <span class="elsevierStyleItalic">msr A</span> and <span class="elsevierStyleItalic">B</span> genes&#46; All the strains were kindly provided by Genoveva Pensado &#40;Bacteriology and Virology department&#41;&#46; Ultrapure RNAse&#47;DNAse free water was used as negative control in all PCR reactions&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pulsed field gel electrophoresis &#40;PFGE&#41;&#46;</span> DNA macro-restriction with the <span class="elsevierStyleItalic">Sma</span>I enzyme and further separation of fragments by pulsed field gel electrophoresis &#40;PFGE&#41; were carried out using a previously described protocol<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">24</span></a>&#46; The obtained profiles were analyzed by the unweighted pair group method with arithmetic average &#40;UPGMA&#41; using <span class="elsevierStyleItalic">BioNumerics</span> v&#46;7&#46;1&#46; The isolates that showed &#8805;80&#37; similarity were included into the same pulsogroup &#40;PG&#41;&#44; while those that showed &#8805;95&#37; similarity were considered to be of identical pulsotype &#40;PT&#41;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">9</span></a>&#46; <span class="elsevierStyleItalic">S&#46; aureus</span> subsp&#46; <span class="elsevierStyleItalic">aureus</span> &#40;strain NCTC 8325&#41; was included as reference size marker&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Source of analyzed <span class="elsevierStyleItalic">S&#46; aureus</span> isolates and resistance phenotypes</span><p id="par0060" class="elsevierStylePara elsevierViewall">We studied 100 isolates of <span class="elsevierStyleItalic">S&#46; aureus</span>&#46; Twenty-three of them were recovered from invasive diseases including bacteremia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#59; 43&#46;4&#37;&#41;&#44; ventilator-associated pneumonia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#59; 35&#37;&#41;&#44; deep abscesses &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#59; 17&#46;3&#37;&#41; and acute meningoencephalitis &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#59; 4&#46;3&#37;&#41;&#46; On the other hand&#44; 77 isolates were recovered from skin and soft tissue infections &#40;SSTIs&#41; including superficial abscesses &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#59; 50&#37;&#41;&#44; wounds &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#59; 28&#46;5&#37;&#41;&#44; cellulitis &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#59; 14&#46;2&#37;&#41; and whitlows &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#59; 6&#46;4&#37;&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Fifty-three isolates were classified as MSSA and the remaining 47 as MRSA &#40;all of them carried the <span class="elsevierStyleItalic">mecA</span> gene&#41;&#59; 25 corresponded to CA-MRSA and 22 to HA-MRSA&#44; according to the above described abbreviated criterion&#46; The distribution of the SCC<span class="elsevierStyleItalic">mec</span> types in HA-MRSA was as follows&#58; SCC<span class="elsevierStyleItalic">mec</span> type I&#44; 5 isolates&#59; SCC<span class="elsevierStyleItalic">mec</span> type II&#44; 15 isolates and SCC<span class="elsevierStyleItalic">mec</span> type III&#44; 2 isolates&#46; Fifteen percent of the MSSA isolates were resistant to MLS<span class="elsevierStyleInf">B</span> antibiotics&#44; whereas this figure increased to 63&#46;8&#37; in the MRSA &#40;CA-MRSA and HA-MRSA&#41; isolates&#46; All <span class="elsevierStyleItalic">S&#46; aureus</span> isolates included in this study were susceptible to vancomycin and teicoplanin&#46; Four isolates &#40;4&#37;&#41; were resistant to rifampicin&#44; all of them carrying the SCC<span class="elsevierStyleItalic">mec</span> type II&#46; Twenty two out of 47 &#40;46&#46;8&#37;&#41; MRSA showed resistance to ciprofloxacin &#40;HA-MRSA&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; CA-MRSA&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46; However&#44; only 4 out of 53 &#40;7&#46;5&#37;&#41; MSSA were resistant to this antibiotic&#46; Eight <span class="elsevierStyleItalic">S&#46; aureus</span> isolates &#40;8&#37;&#41; showed resistance to gentamicin&#44; 4 &#40;7&#46;5&#37;&#41; corresponded to MSSA isolates and 4 &#40;8&#46;5&#37;&#41; to MRSA &#40;HA-MRSA&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#59; CA-MRSA&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46; One methicillin-susceptible isolate was resistant to tetracycline&#46; The only <span class="elsevierStyleItalic">S&#46; aureus</span> isolate that showed resistance to trimethoprim-sulfamethoxazole belonged to the HA-MRSA group&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the resistant phenotypes to MLS<span class="elsevierStyleInf">B</span> antibiotics found in MRSA and MSSA isolates&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the percentage of resistance to macrolides and lincosamides found in MRSA &#40;HA-MRSA&#44; CA-MRSA&#41; and MSSA isolates&#46; Three out of the 10 isolates with iMLS<span class="elsevierStyleInf">B</span> resistance showed the D&#43; phenotype in the disk-diffusion test&#46; The isolates with the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#59; 5 CA-MRSA and 5 MSSA&#41; showed MICs for CLI &#8804;0&#46;125<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml and those with phenotype S &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>62&#59; MSSA 45 and CA-MRSA 17&#41; had MICs for CLI &#8804;0&#46;25<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#46; In those isolates that exhibited the cMLS<span class="elsevierStyleInf">B</span> resistance phenotype &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#59; HA-MRSA&#44; 21 and MSSA&#44; 1 isolate&#41; MICs for CLI were &#8805;256<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#46; As shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; the combination of 2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml of CLI plus 0&#46;12<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml of ERY in the BM assay allowed us to differentiate between isolates displaying iMLS<span class="elsevierStyleInf">B</span> or cMLS<span class="elsevierStyleInf">B</span> resistance phenotypes and those with the MS<span class="elsevierStyleInf">B</span> or S phenotype&#46; Seven out of 10 isolates that showed the iMLS<span class="elsevierStyleInf">B</span> resistant phenotype &#40;D&#44; 4 isolates and D&#43;&#44; 3 isolates&#41; grew in the presence of CLY at 8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml plus ERY 0&#46;12<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml and all the isolates &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41; that showed the cMLS<span class="elsevierStyleInf">B</span> resistance phenotype &#40;HD and R&#41; grew in the presence of the combination 8<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml of CLI plus ERY 0&#46;12<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Distribution of the resistance genes to MLS<span class="elsevierStyleInf">B</span> antibiotics among <span class="elsevierStyleItalic">S&#46; aureus</span> isolates</span><p id="par0070" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; all the isolates that showed the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype in the D-test carried the combination of the <span class="elsevierStyleItalic">ermA</span> and <span class="elsevierStyleItalic">ermC</span> genes&#46; Instead&#44; in those isolates that displayed the cMLS<span class="elsevierStyleInf">B</span> resistance phenotype &#40;HD or R&#41; the predominant genotype was <span class="elsevierStyleItalic">ermA</span> &#40;alone or in combination with other resistance genes&#41;&#46; In those isolates that showed the cMLS<span class="elsevierStyleInf">B</span> &#40;HD&#41; phenotype&#44; the combination of the <span class="elsevierStyleItalic">ermA</span> and <span class="elsevierStyleItalic">mrs</span> genes was seen more frequently &#40;6 out of 8&#41; than in those that displayed the cMLS<span class="elsevierStyleInf">B</span> &#40;R&#41; phenotype &#40;2 in 14&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The <span class="elsevierStyleItalic">ermB</span> gene was found in just one isolate with the cMLSB resistance phenotype&#46; The responsible genotype was not studied in the CA-MRSA isolate that showed the L resistance phenotype&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Sma</span>I-<span class="elsevierStyleItalic">PFGE profiles in MRSA and MSSA isolates&#46;</span> As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#44; the <span class="elsevierStyleItalic">Sma</span>I-PFGE profile analysis of MRSA isolates revealed a wide variety of PTs &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>41&#41; and 3 clusters &#40;pulsogroups&#44; PG&#58; A&#44; B and C&#44; with &#8805;80&#37; similarity and more than 2 isolates in each&#41;&#46; Cluster A included 6 isolates&#44; one with SCC<span class="elsevierStyleItalic">mec</span> IV&#44; one with SCC<span class="elsevierStyleItalic">mec</span> III&#44; one with SCC<span class="elsevierStyleItalic">mec</span> I and finally 3 isolates that carried the SCC<span class="elsevierStyleItalic">mec</span> II element with the cMLSB resistance phenotype that showed 100&#37; identity and were recovered from 3 inpatients located in the same surgery ward&#46; The only isolate with the L resistance phenotype recovered in this study was located in this PG&#46; Cluster B &#40;9 isolates&#41; included 8 CA-MRSA isolates&#46; Three of them &#40;including an isolate carrying the SCC<span class="elsevierStyleItalic">mec</span> type II&#41; showed 100&#37; similarity and were visually identical to the main pulsotype found in local CA-MRSA isolates recovered in Uruguay between 2001 and 2002 &#40;PFGE profile A1&#44; type USA1100&#41;&#46; Other 3 isolates in this PG showed 100&#37; similarity among them &#40;including the single CA-MRSA isolate with the cMLS<span class="elsevierStyleInf">B</span> resistance phenotype recovered in this study&#41; and were also visually similar to the CA-MRSA PFGE profile A1&#46; Cluster C also included CA-MRSA isolates&#46; The 5 CA-MRSA isolates that displayed the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype belonged to 5 different PTs &#40;see <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In the MSSA isolates&#44; 52 PTs and 3 PGs &#40;A&#44; B and C&#44; &#8805;80&#37; similarity&#44; more than 2 isolates in each&#41; &#40;see <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; were recognized&#46; Only 2 isolates showed 95&#37; similarity and were located in the PG C&#46; This PG included 7 isolates&#44; 2 of them with the iMLS<span class="elsevierStyleInf">B</span> phenotype &#40;see <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Clindamycin has been used for the treatment of severe staphylococcal diseases&#44; taking into account some of its pharmacological properties&#46; However&#44; resistance can develop in isolates with the iMLS<span class="elsevierStyleInf">B</span> phenotype&#44; and spontaneous constitutively resistant mutants have arisen from such isolates during clindamycin therapy&#44; determining therapeutic failures in some patients<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a>&#46; This is the first local report about the distribution of resistance phenotypes to MLS<span class="elsevierStyleInf">B</span> antibiotics and their responsible genes in a set of <span class="elsevierStyleItalic">S&#46; aureus</span> isolates recovered from adult inpatients in a public hospital&#46; The overall prevalence of resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics was 38&#37;&#46; This figure is similar to that reported by Abbas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">1</span></a> &#40;40&#37;&#41; in a study conducted in India that included 500 isolates of <span class="elsevierStyleItalic">S&#46; aureus</span> recovered in a tertiary hospital and otherwise higher than that also found in India by Prabhu et al&#46; &#40;28&#46;42&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">25</span></a>&#46; Similarly to what happened in Serbia and India&#44; in the current study most <span class="elsevierStyleItalic">S&#46; aureus</span> isolates &#40;62&#37;&#41; showed susceptibility to both macrolide and lincosamide antibiotics&#46; However&#44; the distribution of the resistance phenotypes was different from that reported by those authors&#46; In Serbia&#44; iMLS<span class="elsevierStyleInf">B</span> was the most frequent resistance phenotype detected &#40;31&#46;5&#8211;33&#46;7&#37;&#41;&#59; instead in India it was MS<span class="elsevierStyleInf">B</span> &#40;17&#37;&#41; followed by both cMLS<span class="elsevierStyleInf">B</span> and iMLS<span class="elsevierStyleInf">B</span> resistance phenotypes &#40;11&#46;6&#37; and 10&#46;8&#37;&#44; respectively&#41;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">21&#44;25</span></a>&#46; In this study the overall data show that the predominant resistance phenotype was cMLS<span class="elsevierStyleInf">B</span> &#40;22&#37;&#41; followed by iMLS<span class="elsevierStyleInf">B</span> &#40;10&#37;&#41;&#44; MS<span class="elsevierStyleInf">B</span> &#40;5&#37;&#41; and L &#40;1&#37;&#41;&#46; Similar figures were reported by Sedaghat in the Iranian teaching hospital and also by Paz Pereira et al&#46; in neighboring Brazil<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#44;28</span></a>&#46; The cMLS<span class="elsevierStyleInf">B</span> resistance phenotype prevailed among HA-MRSA isolates &#40;SCC<span class="elsevierStyleItalic">mec</span> I&#44; II and III&#41; &#40;20&#47;22&#59; 91&#37;&#41;&#44; which is in concordance with similar studies carried out in other countries<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">2&#44;5&#44;29&#44;39</span></a>&#46; In this work the prevalence of the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype was similar among MRSA &#40;CA-MRSA and HA-MRSA&#41; &#40;5&#47;47&#59; 10&#46;6&#37;&#41; and MSSA &#40;5&#47;53&#59; 9&#37;&#41; isolates&#46; This result is not in concordance with the findings reported by Abbas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">1</span></a> or Rahbar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">26</span></a>&#44; which showed a higher prevalence of the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype in MSSA isolates&#46; Furthermore&#44; in contrast to the findings of Mi&#353;ic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">21</span></a> in Serbia&#44; none of the HA-MRSA &#40;SCC<span class="elsevierStyleItalic">mec</span> I&#44; II and III&#41; isolates studied here showed the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The prevalence of MSSA isolates with the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype found in our study &#40;9&#37;&#41; was lower than that reported by Shoji et al&#46; in Japan &#40;25&#46;4&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">30</span></a>&#46; As we will comment below&#44; the results obtained by <span class="elsevierStyleItalic">Sma</span>I-PFGE showed great genetic diversity in both MSSA and MRSA isolates with iMLS<span class="elsevierStyleInf">B</span> and cMLS<span class="elsevierStyleInf">B</span> resistance phenotypes &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46; This suggests a broad diffusion of the responsible resistance genes rather than the circulation of a predominant PT&#46; The overall prevalence of the MS<span class="elsevierStyleInf">B</span> resistance phenotype was 5&#37;&#59; this figure being lower than that reported by Mi&#353;ic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">21</span></a> in Serbia &#40;17&#46;6&#37;&#41; but similar to the results &#40;6&#37;&#41; obtained by Sedaghat et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> in the Iranian teaching hospitals<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">21&#44;28</span></a>&#46; The combination of <span class="elsevierStyleItalic">msrA</span> and <span class="elsevierStyleItalic">msrB</span> genes was detected in all &#40;5&#41; isolates that showed this resistance phenotype&#46; Only one isolate showed the L resistance phenotype&#59; as formerly seen in Argentina&#44; which corresponded to a CA-MRSA isolate carrying SCC<span class="elsevierStyleItalic">mec</span> type IV<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a>&#46; The occurrence of this resistance type remains low at the HP hospital &#40;1&#37;&#41; as was described previously<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">17&#44;21&#44;23</span></a>&#46; The prevalence of resistance phenotypes to MLS<span class="elsevierStyleInf">B</span> antibiotics vary depending on the analyzed country&#44; geographic area and even the type of patient &#40;inpatients vs&#46; outpatients&#59; hospital vs&#46; community origin&#59; children vs&#46; adults&#59; public vs&#46; private institutions&#59; patients or healthcare workers included&#44; among others&#41;&#46; This global trend highlights the need for each country&#44; region or hospital to use its own bacterial resistance surveillance program<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">2&#44;5&#44;26&#44;29</span></a>&#46; The obtained results in the BM assay combining 2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml of CLI plus 0&#46;12<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml of ERY allowed us to differentiate between isolates displaying iMLS<span class="elsevierStyleInf">B</span> or cMLS<span class="elsevierStyleInf">B</span> phenotypes and those with the MS<span class="elsevierStyleInf">B</span> or the S phenotype&#46; However&#44; in contrast with Steward et al&#46;&#8217;s findings<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a>&#44; in this study some <span class="elsevierStyleItalic">S&#46; aureus</span> isolates with an iMLS<span class="elsevierStyleInf">B</span> resistance phenotype and positive D test were able to grow at higher concentrations of clindamycin&#46; This could be partly explained by the fact that these isolates with the D or D&#43; phenotype carry the combination of <span class="elsevierStyleItalic">erm</span> and <span class="elsevierStyleItalic">msr</span> genes&#44; as we discussed further<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a>&#46; All analyzed <span class="elsevierStyleItalic">S&#46; aureus</span> isolates &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#41; were susceptible to vancomycin and teicoplanin&#46; However&#44; it is necessary to conduct an active surveillance to early detect the presence of glycopeptide-resistant strains&#46; As expected&#44; most of the <span class="elsevierStyleItalic">S&#46; aureus</span> isolates grouped in this study as HA-MRSA &#40;21 of 22&#41; showed ciprofloxacin resistance&#46; Only 4 of 100 isolates were resistant to rifampicin and all of them corresponded to HA-MRSA&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Resistance genes to MLS<span class="elsevierStyleInf">B</span> antibiotics and genetic comparison by SmaI-PFGE</span><p id="par0125" class="elsevierStylePara elsevierViewall">The PCR analysis identified the <span class="elsevierStyleItalic">ermA</span> gene as the most frequent MLS<span class="elsevierStyleInf">B</span> resistance gene followed by <span class="elsevierStyleItalic">ermC</span>&#46; The <span class="elsevierStyleItalic">ermA</span> gene was detected individually or in combination with other genes such as <span class="elsevierStyleItalic">ermC</span>&#44; <span class="elsevierStyleItalic">msrA</span> and <span class="elsevierStyleItalic">msrB</span> in 30 &#40;79&#37;&#41; out of 38 <span class="elsevierStyleItalic">S&#46; aureus</span> resistant to MLS<span class="elsevierStyleInf">B</span> antibiotics&#46; In 12 of them&#44; especially in HA-MRSA &#40;11&#47;14&#41;&#44; it was individually detected and all these isolates showed a cMLS<span class="elsevierStyleInf">B</span> resistance phenotype &#40;R&#41; &#40;see <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; This result is in concordance with previous findings obtained in European hospitals<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">27</span></a>&#46; In general&#44; the <span class="elsevierStyleItalic">ermA</span> genes are mainly detected in MRSA isolates and are located in transposons related to Tn554&#44; while the <span class="elsevierStyleItalic">ermC</span> genes are frequently responsible for resistance in MSSA and are located in plasmids&#46; Based on the <span class="elsevierStyleItalic">Sma</span>I PFGE results&#44; we can rule out the hypothesis of a broad hospital spread of a single pulsotype with a cMLS<span class="elsevierStyleInf">B</span> resistance phenotype carrying the <span class="elsevierStyleItalic">ermA</span> gene&#46; Only three isolates belonging to cluster A &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; showed 100&#37; similarity&#59; they carried the SCC<span class="elsevierStyleItalic">mec</span> type II and were recovered from three patients of the same ward&#46; This probably corresponded to a case of limited intrahospital cross contamination&#46; In the two above cited studies&#44; there are no data about the genetic comparison of the included strains&#59; therefore&#44; it cannot be ruled out that they pertained to prevalent clones&#46; In similar studies conducted in Brazil and European countries the <span class="elsevierStyleItalic">ermC</span> gene predominated over the <span class="elsevierStyleItalic">ermA</span> gene<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">19&#44;22&#44;37</span></a>&#46; As it occurred in Brazil&#44; we merely detected one resistant isolate that carried the <span class="elsevierStyleItalic">ermB</span> gene and showed the cMLS<span class="elsevierStyleInf">B</span> resistance phenotype<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">7</span></a>&#46; This low prevalence &#40;2&#46;6&#37;&#41; was expected&#44; taking into account that we only included isolates collected from adult patients&#46; This gene is frequently found in <span class="elsevierStyleItalic">S&#46; aureus</span> isolates from animal origin and also in pediatric CA-MRSA isolates<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7&#44;38</span></a>&#46; The PCR analysis identified the <span class="elsevierStyleItalic">msrA</span> and <span class="elsevierStyleItalic">msrB</span> genes&#44; alone or combined&#44; in 16 isolates belonging to the MSSA&#44; CA-MRSA or HA-MRSA categories with iMLS<span class="elsevierStyleInf">B</span>&#44; cMLS<span class="elsevierStyleInf">B</span> and MS<span class="elsevierStyleInf">B</span> resistance phenotypes&#46; An interesting result of this study was the high rate of combination of MLS<span class="elsevierStyleInf">B</span> resistance genes&#46; The most commonly detected profile was <span class="elsevierStyleItalic">ermA</span> plus <span class="elsevierStyleItalic">ermC</span> &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&#44; followed by the combination of <span class="elsevierStyleItalic">ermA</span> plus <span class="elsevierStyleItalic">msrA</span> &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#44; many of which also bore the <span class="elsevierStyleItalic">msrB</span> gene&#46; All isolates with the iMLS<span class="elsevierStyleInf">B</span> resistance phenotype &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41; carried both <span class="elsevierStyleItalic">ermA</span> and <span class="elsevierStyleItalic">ermC</span> genes&#44; and three of them also harbored the <span class="elsevierStyleItalic">msrB</span> gene &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The <span class="elsevierStyleItalic">Sma</span>I-PFGE results showed great genetic diversity in both MSSA and MRSA isolates with iMLS<span class="elsevierStyleInf">B</span> and cMLS<span class="elsevierStyleInf">B</span> resistance phenotypes&#46; They support the wide spread of the resistance genes to MLS<span class="elsevierStyleInf">B</span> antibiotics in these studied clinical <span class="elsevierStyleItalic">S&#46; aureus</span> isolates rather than the circulation of a predominant PT&#46; This study has two limitations&#58; MRSA isolates were considered to be CA-MRSA or HA-MRSA only according to the SCCmec type that they carried and the use of PCR for <span class="elsevierStyleItalic">erm</span> genes does not allow to differentiate between isolates with iMLS<span class="elsevierStyleInf">B</span> or cMLS<span class="elsevierStyleInf">B</span> resistance phenotypes&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusions</span><p id="par0085" class="elsevierStylePara elsevierViewall">The overall prevalence of resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics in this group of clinical <span class="elsevierStyleItalic">S&#46; aureus</span> isolates was 38&#37; and the resistance phenotype distribution was as follows&#58; cMLS<span class="elsevierStyleInf">B</span>&#44; 22&#37;&#59; iMLS<span class="elsevierStyleInf">B</span>&#44; 10&#37;&#59; MS<span class="elsevierStyleInf">B</span>&#44; 5&#37; and L&#44; 1&#37;&#46; In these resistant isolates we detected&#44; <span class="elsevierStyleItalic">ermA</span>&#44; <span class="elsevierStyleItalic">ermC</span>&#44; <span class="elsevierStyleItalic">ermB</span> and <span class="elsevierStyleItalic">mrsA&#47;B</span> genes&#46; The single <span class="elsevierStyleItalic">ermA</span> gene was commonly found in HA-MRSA &#40;SCC<span class="elsevierStyleItalic">mec</span> I&#44; II and III&#41; isolates&#44; mainly in those with a cMLS<span class="elsevierStyleInf">B</span> R resistance phenotype&#59; whereas the combination <span class="elsevierStyleItalic">ermA</span> and <span class="elsevierStyleItalic">ermC</span> was more commonly observed in MSSA or CA-MRSA &#40;SCC<span class="elsevierStyleItalic">mec</span> IV&#41; isolates with inducible resistance expression &#40;iMLS<span class="elsevierStyleInf">B</span> phenotype&#41;&#46; There was a high rate of combination of MLS<span class="elsevierStyleInf">B</span> resistance genes and the obtained patterns by <span class="elsevierStyleItalic">Sma</span>I-PFGE suggest a great genetic diversity in this group of MRSA and MSSA MLS<span class="elsevierStyleInf">B</span> resistant isolates&#46; The obtained results demonstrate the local presence of <span class="elsevierStyleItalic">S&#46; aureus</span> resistant to MLS<span class="elsevierStyleInf">B</span> antibiotics and its most frequently described responsible genes&#46; These isolates &#40;especially those with the inducible resistance phenotype&#44; iMLSB&#41; may be associated with therapeutic failures&#59; therefore&#44; efforts should be directed toward their correct detection using appropriate laboratory tests&#44; particularly among those recovered from hospitalized individuals suffering from comorbidities or receiving immunosuppressive treatment&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Funding</span><p id="par0090" class="elsevierStylePara elsevierViewall">This work was supported by a grant of the Comisi&#243;n Sectorial de Investigaci&#243;n Cient&#237;fica &#40;CSIC&#41;&#44; Universidad de la Rep&#250;blica &#91;program I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>D group 290&#93;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        2 => array:2 [
          "identificador" => "xpalclavsec1278597"
          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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          "titulo" => "Palabras clave"
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        5 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
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        6 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
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        7 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Results"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Source of analyzed S&#46; aureus isolates and resistance phenotypes"
            ]
            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Distribution of the resistance genes to MLS antibiotics among S&#46; aureus isolates"
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          "titulo" => "Discussion"
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              "identificador" => "sec0050"
              "titulo" => "Resistance genes to MLS antibiotics and genetic comparison by SmaI-PFGE"
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          "identificador" => "sec0035"
          "titulo" => "Conclusions"
        ]
        10 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Funding"
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        11 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conflict of interest"
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          "identificador" => "xack485163"
          "titulo" => "Acknowledgements"
        ]
        13 => array:1 [
          "titulo" => "References"
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      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-07-16"
    "fechaAceptado" => "2019-10-21"
    "PalabrasClave" => array:2 [
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          "clase" => "keyword"
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            0 => "<span class="elsevierStyleItalic">Staphylococcus aureus</span>"
            1 => "MLS<span class="elsevierStyleInf">B</span> resistance"
            2 => "D-test"
            3 => "<span class="elsevierStyleItalic">ermA</span>"
            4 => "<span class="elsevierStyleItalic">ermC</span>"
            5 => "<span class="elsevierStyleItalic">msrA</span>&#47;<span class="elsevierStyleItalic">B</span>"
            6 => "<span class="elsevierStyleItalic">Sma</span>I-PFGE"
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            0 => "<span class="elsevierStyleItalic">Staphylococcus aureus</span>"
            1 => "Resistencia a MLSB"
            2 => "D-test"
            3 => "<span class="elsevierStyleItalic">ermA</span>"
            4 => "<span class="elsevierStyleItalic">ermC</span>"
            5 => "<span class="elsevierStyleItalic">msrA&#47;B</span>"
            6 => "SmaI-PFGE"
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    "highlights" => array:2 [
      "titulo" => "Highlights"
      "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0005" class="elsevierStylePara elsevierViewall">The overall prevalence of MLS<span class="elsevierStyleInf">B</span> resistance in this set of <span class="elsevierStyleItalic">S&#46; aureus</span> was 38&#37;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0010" class="elsevierStylePara elsevierViewall">The phenotype distribution was&#58; cMLS<span class="elsevierStyleInf">B</span>&#44; 22&#37;&#59; iMLS<span class="elsevierStyleInf">B</span>&#44; 10&#37;&#59; MS<span class="elsevierStyleInf">B</span>&#44; 5&#37; and L&#44; 1&#37;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">erm</span>A gene was prevalent in HA-MRSA isolates&#44; mainly in those with a cMLS<span class="elsevierStyleInf">B</span> phenotype&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">The combination <span class="elsevierStyleItalic">erm</span>A and <span class="elsevierStyleItalic">erm</span>C genes was prevalent in isolates with inducible resistance&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Sma</span>I-PFGE results suggest a great genetic diversity in this MLS<span class="elsevierStyleInf">B</span> resistant isolates&#46;</p></li></ul></p></span>"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This study was undertaken to investigate the resistance phenotypes to macrolide-lincosamide-streptogramin B &#40;MLS<span class="elsevierStyleInf">B</span>&#41; antibiotics and their associated genotypes in isolates of <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#46; We analyzed one hundred&#44; consecutive&#44; non-duplicate isolates &#40;methicillin-susceptible MSSA&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>53 and methicillin-resistant MRSA&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47&#41; obtained from various clinical samples between July 2012 to December 2013&#46; The resistance profile to MLS<span class="elsevierStyleInf">B</span> antibiotics was determined by phenotypic methods and the resistance genes were detected by PCR assays&#46; All of the isolates were subjected to pulsed-field gel electrophoresis &#40;<span class="elsevierStyleItalic">Sma</span>I-PFGE&#41;&#46; The overall prevalence of resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics was 38&#37; and the resistance phenotype distribution was as follows&#58; cMLS<span class="elsevierStyleInf">B</span>&#44; 22&#37;&#59; iMLS<span class="elsevierStyleInf">B</span>&#44; 10&#37;&#59; MS<span class="elsevierStyleInf">B</span>&#44; 5&#37; and L&#44; 1&#37;&#46; We detected <span class="elsevierStyleItalic">ermA</span>&#44; <span class="elsevierStyleItalic">ermC</span>&#44; <span class="elsevierStyleItalic">ermB</span> and <span class="elsevierStyleItalic">mrsA&#47;B</span> genes in these resistant isolates&#46; The single <span class="elsevierStyleItalic">ermA</span> gene was commonly observed mainly in those with a cMLS<span class="elsevierStyleInf">B</span> R phenotype&#44; whereas the combination <span class="elsevierStyleItalic">ermA</span> and <span class="elsevierStyleItalic">ermC</span> was more commonly observed in isolates with inducible expression&#46; The patterns of <span class="elsevierStyleItalic">Sma</span>I-PFGE suggest a great genetic diversity in both MRSA and MSSA resistant to MLS<span class="elsevierStyleInf">B</span> antibiotics&#46; The results demonstrate the local presence of <span class="elsevierStyleItalic">S&#46; aureus</span> resistant to MLS<span class="elsevierStyleInf">B</span> antibiotics and its most frequently described responsible genes&#46; Some of these isolates&#44; especially those with the iMLS<span class="elsevierStyleInf">B</span> phenotype&#44; may be associated with therapeutic failure&#46; Therefore&#44; efforts should be directed to the correct detection of all MLS<span class="elsevierStyleInf">B</span> resistant isolates using appropriate laboratory tests&#46; PFGE results reveal a wide spread of resistance genes rather than the circulation of <span class="elsevierStyleItalic">S&#46; aureus</span> clones resistant to MLS<span class="elsevierStyleInf">B</span> antibiotics&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Los objetivos de este estudio fueron investigar en <span class="elsevierStyleItalic">Staphylococcus aureus</span> la presencia de fenotipos resistentes a los antibi&#243;ticos macr&#243;lidos&#44; lincosamidas y estreptograminas tipo<span class="elsevierStyleHsp" style=""></span>B &#40;MLS<span class="elsevierStyleInf">B</span>&#41; y conocer sus genotipos responsables&#46; Analizamos 100 aislamientos consecutivos&#44; no duplicados &#40;53 sensibles a meticilina &#91;MSSA&#93; y 47 resistentes a meticilina &#91;MRSA&#93;&#41;&#44; obtenidos entre 2012 y 2013 a partir de diferentes muestras cl&#237;nicas&#46; El perfil de resistencia a los antibi&#243;ticos MLS<span class="elsevierStyleInf">B</span> fue determinado por m&#233;todos fenot&#237;picos y los genes de resistencia se detectaron por PCR&#46; Todos los aislamientos fueron comparados por <span class="elsevierStyleItalic">Sma</span>I-PFGE&#46; La prevalencia global de resistencia a los antibi&#243;ticos MLS<span class="elsevierStyleInf">B</span> fue del 38&#37; y la distribuci&#243;n de los fenotipos de resistencia fue la siguiente&#58; cMLS<span class="elsevierStyleInf">B</span>&#44; 22&#37;&#59; iMLS<span class="elsevierStyleInf">B</span>&#44; 10&#37;&#59; MS<span class="elsevierStyleInf">B</span>&#44; 5&#37;&#59; L&#44; 1&#37;&#46; Se detectaron los genes <span class="elsevierStyleItalic">ermA&#44; ermC</span> y <span class="elsevierStyleItalic">mrsA&#47;B</span> en los aislamientos resistentes&#46; El gen <span class="elsevierStyleItalic">ermA</span> se observ&#243;&#44; sobre todo&#44; en aislamientos con fenotipo resistente constitutivo<span class="elsevierStyleHsp" style=""></span>R &#40;cMLS<span class="elsevierStyleInf">B</span>&#41;&#44; mientras que la combinaci&#243;n <span class="elsevierStyleItalic">ermA</span> y <span class="elsevierStyleItalic">ermC</span> se detect&#243; principalmente en aislamientos con resistencia inducible &#40;iMLS<span class="elsevierStyleInf">B</span>&#41;&#46; Los patrones de <span class="elsevierStyleItalic">Sma</span>I-PFGE sugieren una gran diversidad gen&#233;tica en los aislamientos resistentes a los antibi&#243;ticos MLS<span class="elsevierStyleInf">B</span>&#44; tanto MRSA como MSSA&#46; Los resultados demuestran la presencia local de <span class="elsevierStyleItalic">S&#46; aureus</span> resistentes a los antibi&#243;ticos MLS<span class="elsevierStyleInf">B</span> y de sus genes responsables m&#225;s frecuentemente descritos&#46; Estos cultivos&#44; especialmente aquellos con fenotipo resistente iMLS<span class="elsevierStyleInf">B</span>&#44; pueden asociarse con fallas terap&#233;uticas&#46; Por lo tanto&#44; los esfuerzos deben dirigirse a la correcta detecci&#243;n de todos los cultivos resistentes a MLS<span class="elsevierStyleInf">B</span> utilizando pruebas de laboratorio adecuadas&#46; Los resultados de <span class="elsevierStyleItalic">Sma</span>I-PFGE sugieren una amplia diseminaci&#243;n de genes de resistencia&#44; m&#225;s que la circulaci&#243;n de clones resistentes a los antibi&#243;ticos MLS<span class="elsevierStyleInf">B</span>&#46;</p></span>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Pulsed-field gel electrophoresis &#40;PFGE&#41; dendrogram of methicillin-resistant <span class="elsevierStyleItalic">S&#46; aureus</span> isolates showing PTs&#44; PGs&#44; associated profile of resistance&#44; SCC<span class="elsevierStyleItalic">mec</span> type and sample source&#46; Dashed line indicates PGs &#40;named as A&#44; B and C&#44; with &#8805;80&#37; similarity and more than 2 isolates in each&#41;&#46; cMLS<span class="elsevierStyleInf">B</span>&#44; constitutive resistance to macrolide&#44; lincosamide and type B streptogramin&#59; iMLS<span class="elsevierStyleInf">B</span>&#44; inducible resistance to macrolide&#44; lincosamide and type B streptogramin&#59; MS<span class="elsevierStyleInf">B</span>&#44; resistance to macrolide and streptogramin B&#59; L&#44; resistance to lincosamides&#59; CIP&#44; resistance to ciprofloxacin&#59; GM&#44; resistance to gentamicin&#59; RIF&#44; resistance to rifampicin&#59; SXT&#44; resistance to trimethoprim-sulfamethoxazole&#59; None&#44; susceptible to all tested antibiotics&#46;</p>"
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        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Pulsed-field gel electrophoresis &#40;PFGE&#41; dendrogram of methicillin-susceptible <span class="elsevierStyleItalic">S&#46; aureus</span> isolates showing PTs&#44; PGs&#44; associated profile of resistance and sample source&#46; Dashed line indicates PGs &#40;named as A&#44; B and C&#44; with &#8805;80&#37; similarity and more than 2 isolates in each&#41;&#46; cMLS<span class="elsevierStyleInf">B</span>&#44; constitutive resistance to macrolide&#44; lincosamide and type B streptogramin&#59; iMLS<span class="elsevierStyleInf">B</span>&#44; inducible resistance to macrolide&#44; lincosamide and type B streptogramin&#59; MS<span class="elsevierStyleInf">B</span>&#44; resistance to macrolide and streptogramin B&#59; L&#44; resistance to lincosamides&#59; CIP&#44; resistance to ciprofloxacin&#59; GM&#44; resistance to gentamicin&#59; RIF&#44; resistance to rifampicin&#59; TET&#44; resistance to tetracycline&#59; None&#44; susceptible to all tested antibiotics&#46;</p>"
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MRSA with SCC<span class="elsevierStyleItalic">mec</span> type</th><th class="td" title="\n
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                  \t\t\t\t" scope="col">Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">II n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">III n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t">15&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lincosamides&#40;iMLS<span class="elsevierStyleInf">B</span>&#44; cMLS<span class="elsevierStyleInf">B</span> and L resistance phenotypes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2394235.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics in <span class="elsevierStyleItalic">S&#46; aureus</span> isolates&#46;</p>"
        ]
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      4 => array:8 [
        "identificador" => "tbl0015"
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        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="5" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disk diffusion phenotype results</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">iMLS<span class="elsevierStyleInf">B</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col">cMLS<span class="elsevierStyleInf">B</span><a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a> &#40;HD&#47;R&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">MS<span class="elsevierStyleInf">B</span><a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col">S<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">D&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&#46; of isolates&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;8&#47;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">No&#46; of isolates that grew with</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">CLI 8</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#956;g&#47;ml plus</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ERY 0&#46;12<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ERY 0&#46;06<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ERY 0&#46;03<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">CLI 4</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#956;g&#47;ml plus</span></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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ERY 0&#46;12<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ERY 0&#46;06<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ERY 0&#46;03<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ERY 0&#46;03<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">MIC100 to CLI without ERY</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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          "notaPie" => array:4 [
            0 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Inducible resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics&#44; D&#58; clear zone around the CLI disk near to the ERY disk&#59; D&#43;&#58; like the previous one but with small colonies growing up to the CLI disk in an otherwise clear zone&#46;</p>"
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            1 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">cMLS<span class="elsevierStyleInf">B</span> &#40;HD&#47;R&#41; Constitutive resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics&#44; HD&#58; two zones of growth appear around the CLI disk&#44; one zone is a light growth extending from the CLI disk to the second zone where the growth is much thicker&#59; R&#58; growth to the edge of both the CLI and ERY disks&#46;</p>"
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            2 => array:3 [
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0040">MS<span class="elsevierStyleInf">B</span> clear zone around the CLI disk&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0045">S susceptible to both the CLI and ERY disks&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resistance phenotype in the D-test assay</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col">cMLS<span class="elsevierStyleInf">B</span> &#40;R&#41; <a class="elsevierStyleCrossRef" href="#tblfn0060"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0050">iMLS<span class="elsevierStyleInf">B</span>&#58; inducible resistance to MLS<span class="elsevierStyleInf">B</span> antibiotics&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0075">ND&#44; not done&#44; unknown&#46;</p>"
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                      "titulo" => "Inducible clindamycin and methicillin resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> in a tertiary care hospital&#44; Kathmandu&#44; Nepal"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28693489"
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                            2 => "J&#46; Shetty"
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                            4 => "P&#46; Jain"
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Article information

ISSN: 03257541
Original language: English

DOI:10.1016/j.ram.2019.10.004

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2024 November	3	0	3
2024 October	58	19	77
2024 September	63	53	116
2024 August	46	49	95
2024 July	51	28	79
2024 June	35	13	48
2024 May	36	21	57
2024 April	41	23	64
2024 March	53	20	73
2024 February	60	38	98
2024 January	57	19	76
2023 December	49	15	64
2023 November	96	9	105
2023 October	74	13	87
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2023 August	31	13	44
2023 July	39	4	43
2023 June	75	35	110
2023 May	142	16	158
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2023 March	52	19	71
2023 February	61	32	93
2023 January	55	18	73
2022 December	77	17	94
2022 November	101	9	110
2022 October	113	11	124
2022 September	51	9	60
2022 August	53	13	66
2022 July	37	11	48
2022 June	19	10	29
2022 May	25	11	36
2022 April	24	12	36
2022 March	41	15	56
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2021 December	61	9	70
2021 November	42	10	52
2021 October	55	15	70
2021 September	75	11	86
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2021 July	25	11	36
2021 June	33	13	46
2021 May	67	15	82
2021 April	204	20	224
2021 March	70	6	76
2021 February	47	14	61
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2020 December	55	14	69
2020 November	79	19	98
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2020 August	35	14	49
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