Molecular Mechanism of Polymyxin Resistance in Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli Isolates from Henan Province, China: A Multicenter Study

Wenjuan Yan; Qi Zhang; Yingjie Zhu; Nan Jing; Youhua Yuan; Yi Zhang; Siying Ren; Dongmei Hu; Wenmin Zhao; Xiaojuan Zhang; Caiqin Shi; Meiyun Wang; Yi Li

doi:10.2147/IDR.S314490

Molecular Mechanism of Polymyxin Resistance in Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli Isolates from Henan Province, China: A Multicenter Study

Infect Drug Resist. 2021 Jul 12:14:2657-2666. doi: 10.2147/IDR.S314490. eCollection 2021.

Authors

Wenjuan Yan^#¹, Qi Zhang^#¹, Yingjie Zhu¹, Nan Jing¹, Youhua Yuan¹, Yi Zhang², Siying Ren³, Dongmei Hu⁴, Wenmin Zhao⁵, Xiaojuan Zhang⁶, Caiqin Shi⁷, Meiyun Wang⁸, Yi Li¹

Affiliations

¹ Department of Clinical Microbiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China.
² Department of Clinical Laboratory, Zhengzhou Central Hospital, Affiliated to Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
³ Department of Clinical Laboratory, Kaifeng People's Hospital, Kaifeng, Henan, People's Republic of China.
⁴ Department of Clinical Laboratory, Zhumadian First People's Hospital, Zhumadian, People's Republic of China.
⁵ Department of Clinical Laboratory, Kaifeng Central Hospital, Kaifeng, Henan, People's Republic of China.
⁶ Department of Clinical Laboratory, Gongyi People's Hospital, Zhengzhou, Henan, People's Republic of China.
⁷ Department of Microbiology Laboratory, KingMed Diagnostics, Zhengzhou, Henan, People's Republic of China.
⁸ Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: To evaluate polymyxin-resistant Klebsiella pneumoniae and Escherichia coli prevalence and characteristics in the Henan province, China.

Materials and methods: A total of 2301 bacterial isolates collected at six hospitals were assessed. Their response to polymyxin was evaluated by minimum inhibitory concentration (MIC) analysis, and the mobilized colistin resistance (mcr) and carbapenemase gene were explored. Mutations on mgrB, phoPQ, pmrAB, and crrAB in polymyxin-resistant K. pneumoniae were detected by PCR. phoP, phoQ, pmrK, pmrA, pmrB, and pmrC transcriptional levels were quantified by RT-qPCR. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing were performed to determine the phylogenetic relationship between the polymyxin-resistant isolates.

Results: Of the E. coli and K. pneumoniae isolates identified, 0.3% and 1.4% were polymyxin-resistant, respectively, with MICs of 4-64 μg/mL. All polymyxin-resistant isolates were susceptible to tigecycline. Four E. coli isolates were mcr-1-positive and one was carbapenem-resistant, carrying bla _NDM-5 and mcr-1. One K. pneumoniae isolate was mcr-1-positive and nine were carbapenem-resistant (PRCRKP), carrying bla _KPC-2 but not mcr-1. The five E. coli isolates belonged to four sequence types (ST2, ST132, ST632, and ST983). All PRCRKP isolates belonged to ST11. However, all 16 isolates belonged to different PFGE types with <95% genetic similarity. Insertion sequences in mgrB were detected in nine (81.8%) polymyxin-resistant K. pneumoniae samples. Colistin resistance was linked with pmrHFIJKLM operon upregulation, with phoP, phoQ, and pmrK being overexpressed in all but one of the polymyxin-resistant K. pneumoniae samples. Furthermore, 33.3% of patients carrying polymyxin-resistant isolates had previously used polymyxin, and 66.7% patients displayed good clinical outcomes.

Conclusion: The K. pneumoniae polymyxin resistance rate was slightly higher than that of E. coli and mcr-1 was more common in E. coli than in K. pneumoniae. Moreover, the insertion of ISkpn14 into mgrB may be the main contributor to polymyxin-resistance in K. pneumoniae in Henan.

Keywords: Escherichia coli; Henan province; Klebsiella pneumoniae; mcr; polymyxin.

Grants and funding

This work was supported by the Science and Technology Research Project of Henan Province [grant number SBGJ2018084, SBGJ 201903018 and 202102310355], the Joint Program of Medical Science and Technology Research of Henan Province (LHGJ20190611), and the Collaborative Innovation Major Project of Zhengzhou [grant number 20XTZX05015]. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.