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2012 - 2015年台湾地区碳青霉烯类不敏感菌的耐药机制及分子流行病学

Resistance mechanisms and molecular epidemiology of carbapenem-nonsusceptible in Taiwan, 2012-2015.

作者信息

Chang Ya-Ting, Siu L Kristopher, Wang Jann-Tay, Wu Tsu-Lan, Chen Yu-Hui, Chuang Yin-Ching, Lin Jung-Chung, Lu Po-Liang

机构信息

Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

National Institutes of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.

出版信息

Infect Drug Resist. 2019 Jul 16;12:2113-2123. doi: 10.2147/IDR.S208231. eCollection 2019.

Abstract

PURPOSE

This study aimed to investigate the resistance mechanisms and molecular epidemiology of carbapenem-nonsusceptible (CnsEC) in Taiwan.

PATIENTS AND METHODS

From 2012 to 2015, 237 isolates with minimum inhibitory concentrations of imipenem or meropenem >1 μg/mL were collected in a nationwide surveillance and subjected to polymerase chain reaction (PCR) for carbapenemase, AmpC-type β-lactamase, and extended spectrum β-lactamase (ESBL) genes. We evaluated outer membrane proteins (OmpF and OmpC) loss and conducted multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Isolates that were resistant to all carbapenems were designated as pan-carbapenem-resistant (pCREC) in this study.

RESULTS

The predominant resistance mechanism of CnsEC in Taiwan was the CMY-2 β-lactamase in combination with OmpF and OmpC loss. Sequence type 131 was the most prevalent type (29.2%). Among 237 CnsEC isolates, 106 (44.7%) isolates were pCREC and 18 (7.59%) produced carbapenemase. The prevalence of carbapenemases increased from 6% in 2012 to 11.36% in 2015. Various carbapenemases including KPC-2, IMP-8, NDM-1, NDM-5, VIM-1, OXA-48, and OXA-181 were identified, with NDM-1 being the most common (38.9%) carbapenemase. Comparison between pCREC and non-pCREC among the non-carbapenemase-producing CnsEC isolates revealed SHV, CMY, co-carriage of SHV and CTX-M and concurrent loss of both OmpF and OmpC were more commonly detected in the pCREC group. PFGE revealed no nationwide clonal spread of carbapenemase-producing .

CONCLUSION

NDM-1 was the most common carbapenemase and combination of CMY-2 and concurrent OmpF and OmpC porin loss was the most prevalent resistance mechanism in CnsEC in Taiwan.

摘要

目的

本研究旨在调查台湾地区碳青霉烯不敏感大肠埃希菌(CnsEC)的耐药机制及分子流行病学。

患者与方法

2012年至2015年期间,在一项全国性监测中收集了237株亚胺培南或美罗培南最低抑菌浓度>1μg/mL的菌株,并对其进行碳青霉烯酶、AmpC型β-内酰胺酶和超广谱β-内酰胺酶(ESBL)基因的聚合酶链反应(PCR)检测。我们评估了外膜蛋白(OmpF和OmpC)缺失情况,并进行多位点序列分型和脉冲场凝胶电泳(PFGE)。在本研究中,对所有碳青霉烯类耐药的菌株被指定为泛碳青霉烯耐药(pCREC)。

结果

台湾地区CnsEC的主要耐药机制是CMY-2β-内酰胺酶与OmpF和OmpC缺失共同作用。序列型131是最常见的类型(29.2%)。在237株CnsEC分离株中,106株(44.7%)为pCREC,18株(7.59%)产生碳青霉烯酶。碳青霉烯酶流行率从2012年的6%上升至2015年 的11.36%。鉴定出多种碳青霉烯酶,包括KPC-2、IMP-8、NDM-1、NDM-5、VIM-1、OXA-48和OXA-181,其中NDM-1是最常见的(38.9%)碳青霉烯酶。在不产生碳青霉烯酶的CnsEC分离株中,pCREC与非pCREC之间的比较显示,SHV、CMY、SHV与CTX-M的共同携带以及OmpF和OmpC的同时缺失在pCREC组中更常被检测到。PFGE显示产碳青霉烯酶的菌株在全国范围内没有克隆传播。

结论

NDM-1是最常见的碳青霉烯酶,CMY-2与OmpF和OmpC孔蛋白同时缺失的组合是台湾地区CnsEC中最普遍的耐药机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/6642643/c84e93c75a11/IDR-12-2113-g0001.jpg

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