Colistin-resistance gene mcr in clinical carbapenem-resistant Enterobacteriaceae strains in China, 2014-2019

Abstract

To investigate whether introduction of colistin into the clinical settings selected colistin-resistant CRE, we performed molecular epidemiological study of 1868 CRE strains collected from different geographical locales in China during the period 2014-2019. 1755 (96.18%) isolates carried the carbapenemase genes bla_KPC and bla_NDM; 14 Escherichia coli isolates (0.75%) carrying mcr-1 and bla_NDM (MCR-CREC) were also identified. Importantly, the number and relative prevalence of MCR-CREC isolates increased from 5 (0.41%) to 9 (1.38%) after introduction of polymyxin into clinical practice. Consistently, results of genetic analysis indicated that MCR-CREC strains collected before December 2017 were genetically diverse, yet those collected after that date exhibited more closely related genetic profiles, indicating that specific MCR-CREC strains were rapidly selected as a result of increased usage of colistin in clinical settings. The resistance level of MCR-CREC isolates to colistin increased after the introduction of polymyxin into clinical use with the MIC to colistin from <2 mg/L in 80% strains to 2 mg/L in 100% strains. Further dissemination of MCR-CREC strains, which exhibit resistance to the last-line drugs of carbapenems and colistin, is expected to pose a severe threat to human health.

Keywords: Carbapenem-resistant Enterobacteriaceae; China; clinical uses; colistin; mcr-1.

Figure 1.

Distribution of mcr-1 in carbapenem-resistant Enterobacteriaceae strains in China. mcr-1-producing isolates were denoted with stars. The provinces included in this study are shaded.

Figure 2.

Mid-point rooted phylogeny of mcr-1-bearing E. coli strains. (A) Strains isolated before 1 December 2017 were labelled with grey backgrounds. MLST, O and H serotypes, the presence of antimicrobial resistance genes (AMR) encoding ESBLs, carbapenemases, and MCR-1 were plotted. Year of isolation for each strain was denoted after the dash line.