title: Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study.
abstract: BACKGROUND
  Polymyxin antibiotics are used as last-resort therapies to treat infections caused by multidrug-resistant Gram-negative bacteria. The plasmid-mediated colistin resistance determinant MCR-1 has been identified in Enterobacteriaceae in China. We did this study to investigate the prevalence of the mcr-1 gene in clinical isolates from patients with bloodstream infections in China.
  
  
  METHODS
  Clinical isolates of Escherichia coli and Klebsiella pneumoniae were collected from patients with bloodstream infections at 28 hospitals in China, then screened for colistin resistance by broth microdilution and for the presence of the mcr-1 gene by PCR amplification. We subjected mcr-1-positive isolates to genotyping, susceptibility testing, and clinical data analysis. We established the genetic location of mcr-1 with Southern blot hybridisation, and we analysed plasmids containing mcr-1 with filter mating, electroporation, and DNA sequencing.
  
  
  RESULTS
  2066 isolates, consisting of 1495 E coli isolates and 571 K pneumoniae isolates were collected. Of the 1495 E coli isolates, 20 (1%) were mcr-1-positive, whereas we detected only one (<1%) mcr-1-positive isolate among the 571 K pneumoniae isolates. All mcr-1-positive E coli and K pneumoniae isolates were resistant to colistin, with minimum inhibitory concentrations values in the range of 4-32 mg/L, except for one E coli isolate that had a minimum inhibitory concentration less than or equal to 0·06 mg/L. All 21 mcr-1-positive isolates were susceptible to tigecycline and 20 isolates (95%) were susceptible to the carbapenem and β-lactamase inhibitor combination piperacillin and tazobactam. One mcr-1-positive E coli isolate also produced NDM-5, which confers resistance to beta-lactam antibiotics. The 21 mcr-1-positive isolates were clonally diverse and carried mcr-1 on two types of plasmids, a 33 kb IncX4 plasmid and a 61 kb Inc12 plasmid. The 30 day mortality of the patients with bloodstream infections caused by mcr-1-positive isolates was zero.
  
  
  CONCLUSIONS
  mcr-1-positive isolates from bloodstream infections were rare, sporadic, and remained susceptible to many antimicrobial agents. E coli, rather than K pneumoniae, was the main host of the mcr-1 gene. Further studies are needed to clarify the clinical impact of this novel resistance gene.
  
  
  BACKGROUND
  National Natural Science Foundation of China.
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Quan
authors.affiliation: Centre of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Huichuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Clinical Laboratory Department, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Institute of Translational Medicine, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Infectious Diseases, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Akova
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address: yvys119@163.com.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002681:China / Q000453:epidemiology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000453:epidemiology* / Q000382:microbiology; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D008137:Longitudinal Studies; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics; D015995:Prevalence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins