Dissemination of the mcr-1 colistin resistance gene

Mulvey, Michael R.; Mataseje, Laura; Robertson, James A.; Nash, John H. E.; Boerlin, Patrick; Toye, Baldwin; Irwin, Rebecca; Melano, Roberto G.

doi:10.1016/s1473-3099(16)00067-0

Cited by 94 publications

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“…The 2 multilocus sequence types of the isolates that we identified (ST648 and ST515) were not closely related to the 3 reported by Mulvey and colleagues. 32 In the present study, both E. coli isolates with the mcr-1 gene were recovered from patients seen at hospital emergency departments, which implies community onset of infection. Because details regarding the clinical history of the patients were not available, it is impossible to determine whether the isolates were community-acquired or hospital-acquired.…”

Section: Discussionmentioning

confidence: 60%

“…and K. pneumoniae. 9,12,23,24 Mulvey and colleagues 32 have previously reported on the presence of the mcr-1 gene among E. coli in Canada. They screened about 1600 isolates from Canadian sources and identified 3 E. coli isolates that were mcr-1-positive: 1 was recovered from a clinical specimen in 2011, and 2 were recovered from lean ground beef in 2010.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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...

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…The location of the mcr-1 gene on multidrug resistance plasmids is worrying because the use of antimicrobials other than polymyxins can participate in the coselection of isolates carrying mcr-1 and in their spread. More worryingly, the plasmid-mediated mcr-1 gene has been identified in highly drug-resistant Enterobacteriaceae isolates harboring plasmids encoding carbapenemase genes (bla NDM-1 , bla NDM-5 , bla NDM-9 , bla OXA-48 , bla KPC-2 , and bla VIM-1 ) (146)(147)(148)(149)(150)(151)(152). Note that the mcr-1 gene was recently identified on the chromosome of an E. coli strain in Switzerland, suggesting that this resistance gene might be integrated and therefore stabilized in the genome in some isolates (153).…”

Section: Plasmid-mediated Resistance To Polymyxinsmentioning

confidence: 99%

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

2017

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SUMMARY Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.

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“…The gene has often been reported in strains susceptible to other antibiotics, but occasionally also in multidrug-resistant (MDR) strains (3)(4)(5)(6)(7)(8), including members of highrisk epidemic lineages spreading in the clinical setting (9,10). Thus far, however, it had never been found in Klebsiella pneumoniae strains of clonal group 258 (CG258), which is the lineage mainly responsible for the dissemination of KPC-type carbapenemases on the global scale (11,12).…”

mentioning

confidence: 99%

mcr-1.2 , a New mcr Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPC Carbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512

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Tascini

et al. 2016

Antimicrob Agents Chemother

153

117

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A novel mcr variant, named mcr-1.2, encoding a Gln 3 -to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512 Klebsiella pneumoniae isolate collected in Italy from a surveillance rectal swab from a leukemic child. The mcr-1.2 gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of mcr-1-bearing plasmids previously found in Escherichia coli and K. pneumoniae strains from geographically distant sites (Estonia, China, and South Africa).

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Dissemination of the mcr-1 colistin resistance gene

Abstract: plasmids to other Gram-negative pathogens, which might result in untreatable infections. Thus, the spread of mcr-1, especially into strains that are already resistant to carbapenems, must be stopped.

Cited by 94 publications

References 3 publications

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

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

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

mcr-1.2 , a New mcr Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPC Carbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512

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