Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China: a multicentre case-control and molecular epidemiological study
Authors: Yan Jiang, Ying Zhang, Jun Lu, Qihui Wang, Yushan Cui, Yanfei Wang, Jingjing Quan, Dongdong Zhao, Xiaoxing Du, Haiyang Liu, Xi Li, Xueqing Wu, Xiaoting Hua, Ye Feng, Yunsong Yu
Journal: The Lancet Microbe (2020)

BackgroundAlthough the emergence of the plasmid-mediated colistin resistance gene, mcr-1, caused global concern, little is known about its clinical implications and transmission characteristics over time. We aimed to investigate the clinical relevance of infection with mcr-1-positive Escherichia coli isolates and to investigate long-term plasmid dynamics.MethodsWe did a multicentre case-control study and molecular epidemiological survey of mcr-1-positive E coli infections. E coli isolates from four hospitals in China in 2008 to 2017 were collected and screened for mcr-1 by PCR and Sanger sequencing. Patients with mcr-1-positive E coli infections and matched controls with mcr-1-negative E coli infections were included in a 1:4 ratio, considering age, sex, living environment, comorbidities, antimicrobials used, and clinical sample type as potential risk factors in a regression model. 28-day mortality was also observed. The genomes of all mcr-1-positive E coli were sequenced to explore their genetic background and map IS Apl1 elements. Plasmids carrying mcr-1 were characterised by their resistance profile and incompatibility group.Findings29 100 isolates were collected across all hospitals and during the study period, 300 (1·03%) of which were mcr-1-positive E coli. The overall proportion of mcr-1-positive isolates significantly increased from 0·42% (1 of 240) in 2008 to 1·39% (66 of 4748; p<0·0001) in 2017. Factors related to health-care contact, including receiving cancer care, indwelling central venous catheter, and hospitalisation in the past 3 months, and some sample types (pus secretion and sputum) were significantly associated with mcr-1-positive E coli infection. 28-day mortality was low in both mcr-1-positive (11 [4·4%] of 248 patients) and mcr-1-negative (39 [3·8%] of 1030 patients) groups and did not significantly differ. Although the genetic background of mcr-1-positive E coli was diverse, most of the mcr-1-encoding plasmids occurred in three dominant Inc groups (IncX4, IncI2, and IncHI2). Only the large IncHI2 plasmids conferred multiple resistances and probably integrated with other resistance plasmids. In 205 (68%) of 300 mcr-1-positive E coli isolates, mcr-1 genes lost their capacity for mobilisation because of loss of flanking IS Apl1 elements.InterpretationThe prevalence of mcr-1-positive E coli infection among patients increased over the study period, although it remained low. Health-care contact was the most probable risk factor. Plasmids are likely to have played a critical role in mcr-1 transmission, rather than clone dissemination and lateral transfer of IS Apl1. Our findings underscore the importance of continued surveillance of E coli strains positive for mcr-1 and potentially other resistance-associated genes, particularly in hospital settings.FundingNational Natural Science Foundation of China.