Chang Ya-Ting, Siu L Kristopher, Wang Jann-Tay, Wu Tsu-Lan, Chen Yu-Hui, Chuang Yin-Ching, Lin Jung-Chung, Lu Po-Liang
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
National Institutes of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
Infect Drug Resist. 2019 Jul 16;12:2113-2123. doi: 10.2147/IDR.S208231. eCollection 2019.
This study aimed to investigate the resistance mechanisms and molecular epidemiology of carbapenem-nonsusceptible (CnsEC) in Taiwan.
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.
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 .
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.
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。
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)。
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。
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。