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产NDM-1型广泛耐药大肠杆菌的分子特征及流行病学研究

Molecular Characterization and Epidemiologic Study of NDM-1-Producing Extensively Drug-Resistant Escherichia coli.

作者信息

Du Jia, Li Bin, Cao Jianming, Wu Qing, Chen Huale, Hou Yuanbo, Zhang En, Zhou Tieli

机构信息

1 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang Province, China .

2 School of Medical Lab Science, Wenzhou Medical University , Wenzhou, Zhejiang Province, China .

出版信息

Microb Drug Resist. 2017 Apr;23(3):272-279. doi: 10.1089/mdr.2015.0294. Epub 2016 Jul 6.

Abstract

The emergence and dissemination of NDM-1 (New Delhi metallo-β-lactamase-1)-producing Enterobacteriaceae have resulted in a worldwide public health risk. This study described a high incidence and endemic spread of NDM-1-producing extensively drug-resistant Escherichia coli in a teaching hospital in Zhejiang province, China. We recovered six nonduplicated NDM-1-producing E. coli isolates from May 2014 to August 2014 with positive modified Hodge test and EDTA synergistic test. These isolates were highly resistant to β-lactam antimicrobials, aminoglycosides, and quinolones. PCR and DNA sequences analysis showed that all isolates carried the bla, bla, aac(6')-ib-cr, and qnrB. Several isolates also harbored bla, bla, rmtB, and qnrA. Southern blot confirmed that bla was located on the same ∼55 kb plasmid and conjugation experiments further proved the contransferable characteristic of bla. The ompC sequences showed various mutations, which was related to multidrug resistance in E. coli. Pulsed-field gel electrophoresis identified four of six isolates that belonged to the same genotype. Multilocus sequence typing assigned them to ST2, except one strain that belonged to ST594. Our study demonstrated that the resistance-associated genes and the loss of the outer membrane proteins could account for high resistance of NDM-1-producing E. coli to multiple antimicrobial drugs. Both horizontal transfer of IncN and transmission of ST2 were responsible for the spread of drug resistance. These findings highlighted an urgent need to limit the further dissemination of NDM-1-producing E. coli in this region.

摘要

产NDM-1(新德里金属β-内酰胺酶-1)肠杆菌科细菌的出现和传播已造成全球公共卫生风险。本研究描述了中国浙江省一家教学医院中产NDM-1的广泛耐药大肠杆菌的高发病率和地方性传播。我们在2014年5月至2014年8月期间分离出6株非重复的产NDM-1大肠杆菌,改良 Hodge试验和EDTA协同试验呈阳性。这些分离株对β-内酰胺类抗菌药物、氨基糖苷类和喹诺酮类高度耐药。PCR和DNA序列分析表明,所有分离株均携带bla、bla、aac(6')-ib-cr和qnrB。几株分离株还携带bla、bla、rmtB和qnrA。Southern印迹证实bla位于同一约55 kb质粒上,接合实验进一步证明了bla的可共同转移特性。ompC序列显示出各种突变,这与大肠杆菌的多药耐药性有关。脉冲场凝胶电泳鉴定出6株分离株中有4株属于同一基因型。多位点序列分型将它们归为ST2,只有一株属于ST594。我们的研究表明,耐药相关基因和外膜蛋白的缺失可解释产NDM-1大肠杆菌对多种抗菌药物的高度耐药性。IncN的水平转移和ST2的传播均导致了耐药性的扩散。这些发现凸显了迫切需要限制该地区产NDM-1大肠杆菌的进一步传播。

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