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黎巴嫩革兰氏阴性病原菌中碳青霉烯类耐药机制的异质性:首次全国性横断面研究结果

Heterogeneity of Carbapenem Resistance Mechanisms Among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study.

作者信息

Hammoudi Halat Dalal, Moubareck Carole Ayoub, Sarkis Dolla Karam

机构信息

1 Microbiology Laboratory, School of Pharmacy, Saint-Joseph University , Beirut, Lebanon .

2 Rodolphe Mérieux Laboratory , Beirut, Lebanon .

出版信息

Microb Drug Resist. 2017 Sep;23(6):733-743. doi: 10.1089/mdr.2016.0077. Epub 2017 Jan 12.

DOI:10.1089/mdr.2016.0077
PMID:28080212
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 bla gene 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 bla and bla. 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.

摘要

耐碳青霉烯类革兰氏阴性病原菌已逐渐传播至全球不同国家,成为严重的公共卫生问题。本研究的目的是确定黎巴嫩革兰氏阴性菌中耐碳青霉烯类的流行情况,阐明分子机制,并确定相关菌株的遗传相关性。2012年从黎巴嫩11家医院收集了对碳青霉烯类不敏感的肠杆菌科细菌、鲍曼不动杆菌和铜绿假单胞菌。通过表型试验评估抗菌药物敏感性,通过PCR测序筛选编码碳青霉烯酶的基因,并通过脉冲场凝胶电泳(PGFE)和肠杆菌基因间重复共有序列PCR(ERIC-PCR)检测遗传相关性。共研究了398株非重复的对碳青霉烯类不敏感的分离株,其中44株为肠杆菌科细菌,142株为鲍曼不动杆菌,212株为铜绿假单胞菌。在肠杆菌科细菌中,70.4%的菌株在IncL/M型质粒上携带bla基因,而获得性AmpC头孢菌素酶、超广谱β-内酰胺酶和外排泵是耐碳青霉烯类的其他因素。在鲍曼不动杆菌中,90%产生OXA-23和GES-11,并在bla和bla上游及相邻位置携带插入序列ISAba1。在铜绿假单胞菌中,16%携带VIM-2,4.2%携带IMP-2,1.4%携带IMP-1金属β-内酰胺酶。指纹分析表明,OXA-48样碳青霉烯酶的传播主要通过水平转移介导,而鲍曼不动杆菌中OXA-23和GES-11的扩散以及铜绿假单胞菌中VIM-2的扩散主要是由于克隆传播。本研究是黎巴嫩首次全国范围内对耐碳青霉烯类的调查,显示肠杆菌科细菌的耐药水平较低,而鲍曼不动杆菌和铜绿假单胞菌的耐药水平较高。鉴于该地区目前的变化,持续监测耐碳青霉烯类情况至关重要。

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