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Molecular Mechanisms and Epidemiology of Carbapenem-Resistant Escherichia coli Isolated from Chinese Patients During 2002–2017

Authors Tian X, Zheng X, Sun Y, Fang R, Zhang S, Zhang X, Lin J, Cao J, Zhou T

Received 21 September 2019

Accepted for publication 30 January 2020

Published 17 February 2020 Volume 2020:13 Pages 501—512

DOI https://doi.org/10.2147/IDR.S232010

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Suresh Antony


Xuebin Tian, 1, 2 Xiangkuo Zheng, 2 Yao Sun, 1 Renchi Fang, 1 Siqin Zhang, 1 Xiucai Zhang, 1 Jie Lin, 1 Jianming Cao, 2 Tieli Zhou 1

1Department of Clinical Laboratory, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China

Correspondence: Tieli Zhou
Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
Tel +86-0577-86699370
Email wyztli@163.com

Jianming Cao
School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China
Tel +86-0577-88069595
Email wzcjming@163.com

Background: The emergence and spread of carbapenem-resistant Escherichia coli (E. coli) pose a serious threat to human health worldwide. This study aimed to investigate the molecular mechanisms underlying carbapenem resistance and their prevalence among E. coli in China.
Methods: A collection of 5796 E. coli clinical isolates were collected from the First Affiliated Hospital of Wenzhou Medical University from 2002 to 2017. Sensitivity to antibiotics was determined using the agar dilution method. The detection of carbapenemases production and the prevalence of resistance-associated genes were investigated through modified carbapenem inactivation method (mCIM), PCR and sequencing. The mutations in outer membrane porins genes (ompC and ompF) were also analyzed by PCR and sequencing assays. The effect of efflux pump mechanism on carbapenem resistance was also tested. E. coli were typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).
Results: A total of 58 strains (1.0%) of carbapenem-resistant E. coli were identified. The strains carrying blaKPC-2 and blaNDM accounted for 22.4% (13/58) and 51.7% (30/58), respectively. Among blaNDM- positive strains, 27 blaNDM genes were assigned to blaNDM-5, while the remaining three strains were blaNDM-1, whereas blaVIM, blaIMP, blaOXA-48, and blaSHV were not found. The CTX-M-type β-lactamase genes accounted for 96.6% (56/58). In addition, blaTEM-1 genes were identified in 58.6% of tested strains. In carbapenem-resistant isolates, mutations in OmpC (the majority of mutated sites were D192G and Q104_F141del, accounting for 54.5%) and OmpF (large deletions S75_V127del, W83_D135del and Q88_D135del) were detected. Of note, the antibiotic resistance was not associated with overexpression of efflux pump. Moreover, MLST categorized the 58 carbapenem-resistant isolates into 19 different sequence types. PFGE analysis revealed that homology among the carbapenem-resistant isolates was low and sporadic.
Conclusion: The blaNDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital. blaNDM-5 is becoming a new threat to public health and the alteration of outer membrane porins might help further increase the MIC of carbapenem.

Keywords: Escherichia coli, carbapenem-resistant, carbapenemase, outer membrane porin, epidemiology

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