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How to: screening for mcr-mediated resistance to colistin

Publication at Second Faculty of Medicine |
2022

Abstract

BACKGROUND: Colistin belongs to the last-resort antibiotics. The discovery of a plasmid-bound colistin resistance mediated by the mcr-gene(s) is of great concern since, given its biological potential, there is a risk of its rapid spread.

OBJECTIVES: To discuss the current literature on the methods for the screening of mcr-mediated resistance to colistin. SOURCES: Literature was drawn from a search of PubMed between 1 January 2016 to 26 April 2021.

CONTENT: The selective culture-based or culture-independent approach can be used for the screening of mcr-mediated resistance to colistin in clinical samples. Rapid Polymyxin NP, Colistin Drop or Colistin Agar Spot tests are applicable for the selection of isolates with a suspected resistance to colistin that has to be confimed by broth microdilution.

The mcr-mediated resistance to colistin can be confirmed by the detection of the causal gene(s) or by phenotype using the EDTA-colistin broth disk elution; the production of the MCR-1 enzyme can be confirmed with lateral flow immunoassay, using MALDI-TOF or Liquid chromatography-based mass spectrometry. Whole genome sequencing (WGS) is the ultimate typing method.

When a WGS platform is not available at a healthcare facility, a WGS-outsourced service, in combination with freely available bioinformatics tools, allows for the characterisation of the mcr-gene(s) carrying isolates. IMPLICATIONS: Mcr-mediated colistin resistance should be monitored through active targeted screening.The broth microdilution method is required for colistin susceptibility testing but as only a selected number of clinical isolates are tested, colistin resistance, including mcr-mediated, may remain undetected.

In mcr-1 positive E. coli isolates, the minimal inhibitory concentration (MIC) to colistin can range from 2-8 mg/L, thus it is proposed that Enterobacterales with a colistin MIC of 2 mg/L should be also included in the mcr-mediated colistin resistance screening and those with a confirmed mcr-genotype and/or MCR-phenotype should be considered to be colistin-resistant.