Frequency of MCR-1-mediated colistin resistance among Escherichia coli clinical isolates obtained from patients in Canadian hospitals (CANWARD 2008-2015)

Abstract

Background: Colistin is often used as an antimicrobial of last resort for the treatment of infections caused by multidrug-resistant gram-negative bacilli. In 2015, plasmid-mediated colistin resistance in Escherichia coli due to MCR-1 was described. The purpose of this study was to evaluate the frequency of colistin resistance among E. coli clinical isolates obtained from patients in Canadian hospitals as part of the Canadian Ward Surveillance Study (CANWARD) and to determine how often the mcr-1 gene is detected among the colistin-resistant subset. Methods:From January 2008 to December 2015 (excluding 2011), 10 to 15 sentinel hospitals submitted consecutive clinical isolates (1 per patient per infection site) from blood (100-240), respiratory (100-150), urine (25-100) and wound (25-100) infections. We performed susceptibility testing using Clinical and Laboratory Standards Institute broth microdilution methods. Isolates that showed resistance to colistin as defined by European Committee on Antimicrobial Susceptibility Testing breakpoints (minimum inhibitory concentration ≥ 4 µg/mL) were evaluated for the mcr-1 gene by polymerase chain reaction. Results:In total, 5571 E. coli clinical isolates were obtained over the study years. Twelve isolates (0.2%) were resistant to colistin. The proportion of colistin-resistant isolates varied from 0.0% to 0.5% depending on the study year, and there was no clear trend toward increasing resistance over time. Typically the colistin-resistant isolates remained susceptible to antimicrobials from several other classes. Two colistin-resistant isolates (0.04%) were found to harbour the mcr-1 gene. Interpretation:The results suggest that colistin resistance among E. coli human clinical isolates, including resistance mediated by the mcr-1 gene, remains rare in Canada. AbstractResearch Research CMAJ OPEN E642CMAJ OPEN, 4(4)to MCR-1. MCR-1 (encoded for by the mcr-1 gene) is a member of the phosphoethanolamine transferase enzyme family. It confers resistance to colistin by the transfer of phosphoethanolamine to lipid A, thereby reducing the affinity of the target (by reducing the negative charge) for this polycationic antimicrobial. 7 E. coli isolates with the mcr-1 gene typically have colistin minimum inhibitory concentrations (MICs) in the range of 4 to 8 µg/mL. 7-11The location of the mcr-1 gene on a plasmid is concerning, as this raises the possibility that the resistance determinant may be transferred to multidrug-resistant gram-negative bacteria. Indeed, the mcr-1 gene has already been detected in multidrugresistant E. coli isolates that also contain an extended-spectrum β-lactamase or a carbapenemase enzyme.12-15 Plasmid-mediated colistin resistance attributed to a second mcr gene (mcr-2) has also recently been described. 16 Many clinical microbiology laboratories do not test colistin routinely against E. coli, so the frequency with which resistance occurs in Canada is difficult to estimate from local data. The purpose of this study was to evaluate the frequency of colistin res...

Fecal Carriage and Molecular Epidemiology of mcr-1-Harboring Escherichia Coli from Children in Southern China.

“…Further research is needed with larger cohorts from different geographic locations, representative populations, and demographics to fully understand the prevalence of mcr-1 in our local context. The 21 mcr-1 positive strains detected in this study had MICs of only 4-8 mg/L, which was lower than that of previously reported mcr-carrying Enterobacteriaceae bacteria (MICs of 4-16 mg/L), which showed moderate level of colistin resistance [17]. These results indicate that the resistance level of colistin in E. coli from children was different from that of adults.…”

The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli

“…Thirteen colistin-resistant clinical isolates were tested (Table 4), including P. aeruginosa, A. baumannii, K. pneumoniae, E. coli, and E. cloacae. Notably, the two E. coli isolates in the panel were known to harbor the mcr-1 gene plasmid that transcribe phosphoethanolamine transferase to confer colistin resistance (18). According to the Clinical and Laboratory Standards Institute (CLSI) (28), an MIC of Յ2 g/ml against P. aeruginosa and A. baumannii denotes susceptibility to colistin, while no breakpoint is currently established against Enterobacteriaceae.…”

“…Bacterial strains from CANWARD were clinical specimens collected from patients suffering from a presumed infectious diseases admitted in a participating medical center across Canada. The two colistin-resistant E. coli strains from the CANWARD study had been reported to harbor the plasmid-mediated colistin resistance gene mcr-1, but not mcr-2 (18). The efflux-deficient P. aeruginosa strains PAO200 and PAO750 were obtained from previous studies (41,42).…”

A repeated cross‐sectional study of the epidemiology of Campylobacter and antimicrobial resistant Enterobacteriaceae in free‐living Canada geese in Guelph, Ontario, Canada

“…All isolates were sequence type ST3521, and varied between 1 and 4 SNVs with 98.7% of the core genome analysed. The E. coli geese cluster differed by >12,000 SNVs when compared to nine colistin‐resistant E. coli isolates identified in humans from hospitals identified in the CANWARD study between 2007 and 2016 (Walkty et al, ).…”