title: Heterogeneity of Carbapenem Resistance Mechanisms Among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study.
abstract: Carbapenem-resistant Gram-negative pathogens have progressively disseminated to different countries worldwide, presenting a serious public health concern. The aims of this study were to determine the prevalence of carbapenem resistance in Gram-negative bacteria in Lebanon, to elucidate molecular mechanisms, and to identify genetic relatedness of incriminated strains. Carbapenem nonsusceptible Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas were collected from 11 Lebanese hospitals in 2012. Antimicrobial susceptibility was assessed with phenotypic tests, genes encoding carbapenemases were screened via PCR-sequencing, and genetic relatedness was examined by PGFE and ERIC-PCR. A total of 398 nonrepetitive carbapenem nonsusceptible isolates were studied, of which 44 were Enterobacteriaceae, 142 were A. baumannii, and 212 were Pseudomonas. Among Enterobacteriaceae, 70.4% carried blaOXA-48-likegene on IncL/M-type plasmids, while acquired AmpC cephalosporinases, extended-spectrum-β-lactamases, and efflux-pump were additional contributors to carbapenem resistance. Among A. baumannii, 90% produced OXA-23 and GES-11 and carried insertion sequence ISAba1 upstream and adjacent to blaOXA-23and blaAcinetobacter-derived cephalosporinases. Among Pseudomonas, 16% harbored VIM-2, 4.2% IMP-2, and 1.4% IMP-1 metallo-β-lactamases. Fingerprint analysis indicated that the spread of OXA-48-like carbapenemases was mostly mediated by horizontal transfer, while OXA-23 and GES-11 diffusion in A. baumannii and VIM-2 diffusion in P. aeruginosa were primarily due to clonal dissemination. This study is the first nationwide investigation of carbapenem resistance in Lebanon, showing low level of resistance in Enterobacteriaceae, and higher levels in A. baumannii and Pseudomonas. With current changes in the region, continuous surveillance of carbapenem resistance is crucial.
authors.affiliation: 1 Microbiology Laboratory, School of Pharmacy, Saint-Joseph University , Beirut, Lebanon .|2 Rodolphe Mérieux Laboratory , Beirut, Lebanon .|3 Department of Pharmaceutical Sciences, School of Pharmacy, Lebanese International University , Beirut and Bekaa, Lebanon .
authors.forename: Dalal
authors.initials: D
authors.lastname: Hammoudi Halat
authors.affiliation: 1 Microbiology Laboratory, School of Pharmacy, Saint-Joseph University , Beirut, Lebanon .|2 Rodolphe Mérieux Laboratory , Beirut, Lebanon .|4 College of Natural and Health Sciences, Zayed University , Dubai, United Arab Emirates .
authors.forename: Carole Ayoub
authors.initials: CA
authors.lastname: Moubareck
authors.affiliation: 1 Microbiology Laboratory, School of Pharmacy, Saint-Joseph University , Beirut, Lebanon .|2 Rodolphe Mérieux Laboratory , Beirut, Lebanon .
authors.forename: Dolla Karam
authors.initials: DK
authors.lastname: Sarkis
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007861:Lebanon; D008826:Microbial Sensitivity Tests / Q000379:methods; D010957:Plasmids / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases; C063912:carbapenemase
keywords: Lebanon; beta-lactamases; carbapenemases; epidemiology