Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study

• Published in: The Lancet infectious diseases Vol. 17; no. 4; pp. 400 - 410
• Main Authors: Quan, Jingjing, MS, Li, Xi, PhD, Chen, Yan, PhD, Jiang, Yan, PhD, Zhou, Zhihui, PhD, Zhang, Huichuan, MS, Sun, Lu, MS, Ruan, Zhi, PhD, Feng, Ye, PhD, Akova, Murat, MD, Yu, Yunsong, Prof
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.04.2017; Elsevier Limited
• Subjects: Amides; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial activity; Antimicrobial agents; Bacteria; Bacterial Proteins - genetics; Bacteriology; China - epidemiology; Clinical outcomes; Correlation analysis; Data analysis; Deoxyribonucleic acid; DNA; Drug resistance; Drug Resistance, Bacterial - genetics; E coli; Electroporation; Enterobacteriaceae; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - isolation & purification; Escherichia coli Infections - epidemiology; Escherichia coli Infections - microbiology; Gene sequencing; Genes; Genotype; Gram-negative bacteria; Hospitals; Humans; Impact resistance; Infections; Infectious Disease; Infectious diseases; Klebsiella; Klebsiella Infections - epidemiology; Klebsiella Infections - microbiology; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - isolation & purification; Longitudinal Studies; Microbial Sensitivity Tests; Multidrug resistance; Mutation; Patients; Plasmids; Plasmids - genetics; Prevalence; Public health; Studies; Urogenital system; β-Lactam antibiotics; China; United States > US
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(16)30528-X

Summary 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. Findings 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. Interpretation 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. Funding National Natural Science Foundation of China.