Active surveillance of the spread of mcr-1-positive E coli

In The Lancet Microbe, Yan Jiang and colleagues1Jiang Y Zhang Y Lu J et al.Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China: a multi-centre case-control and molecular epidemiological study.Lancet Microbe. 2020; 1: e24-e33Summary Full Text Full Text PDF Scopus (8) Google Scholar present the results of a retrospective study of the prevalence and emergence of mcr-1 positive Escherichia coli in hospitalised patients in China in the decade between 2008 and 2017. Generally, the overall the proportion of isolates positive for mcr-1 remained low in more than 29 000 clinical E coli isolates; however, a trend of increasing prevalence (from 0·42% in 2008, to 1·39% in 2017) was observed that was consistent with mcr-1 prevalence in humans reported by another research group.2Wang Y Tian GB Zhang R et al.Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study.Lancet Infect Dis. 2017; 17: 390-399Summary Full Text Full Text PDF PubMed Scopus (198) Google Scholar To date, horizontal gene transfer has been considered to be the major driving force of mcr-1 dissemination.3Shen Y Wu Z Wang Y et al.Heterogeneous and flexible transmission of mcr-1 in hospital-associated Escherichia coli.mBio. 2018; 9: e00943-e01018Crossref PubMed Scopus (32) Google Scholar Plasmids carrying mcr-1 belong to different incompatibility groups in different regions and hospitals and need further characterisation. The newly published study also elaborates on the potential risk factors and outcomes of infection in patients infected with mcr-1-positive and mcr-1-negative E coli, such as health-care contact and antibiotic usage history, which was consistent with previous studies.2Wang Y Tian GB Zhang R et al.Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study.Lancet Infect Dis. 2017; 17: 390-399Summary Full Text Full Text PDF PubMed Scopus (198) Google Scholar mcr-1, the first mobile colistin resistance gene mediated by plasmids, was discovered almost 5 years ago.4Liu YY Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2016; 16: 161-168Summary Full Text Full Text PDF PubMed Scopus (2725) Google Scholar Since then, an increasing number of mcr-1 variants have been identified in a variety of bacteria species, which bring new concerns to the field, because some variants could mediate medium to high levels of resistance to colistin.5Sun J Zhang H Liu YH et al.Towards understanding MCR-like colistin resistance.Trends Microbiol. 2018; 26: 794-808Summary Full Text Full Text PDF PubMed Scopus (216) Google Scholar Although many studies have shown the global prevalence of mcr-1 in health-care systems, communities, agriculture, and the environment, only a few retrospective studies have been done on the emergence and prevalence of mcr-1 before its discovery. One retrospective study6Liu X Wang Y Cui L et al.A retrospective study on mcr-1 in clinical Escherichia coli and Klebsiella pneumoniae isolates in China from 2007 to 2016.J Antimicrob Chemother. 2018; 73: 1786-1790PubMed Google Scholar traced the emergence of mcr-1 back to 2011–12, whereas Jiang and colleagues1Jiang Y Zhang Y Lu J et al.Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China: a multi-centre case-control and molecular epidemiological study.Lancet Microbe. 2020; 1: e24-e33Summary Full Text Full Text PDF Scopus (8) Google Scholar identified the emergence of mcr-1 as having occurred as early as 2008 in Zhejiang province; however, this study only included hospitals from four cities in China. Retrospective studies have been few in number and are often limited by small demographic regions and numbers of cases, making it difficult to trace the early emergence of mcr-1 after colistin was reintroduced in the clinical practice for the treatment of multidrug-resistant Gram-negative bacterial infections in the early 2000s.7Li J Nation RL Turnidge JD et al.Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections.Lancet Infect Dis. 2006; 6: 589-601Summary Full Text Full Text PDF PubMed Scopus (958) Google Scholar Retrospective studies of livestock are even rarer than those in clinical settings, because most antimicrobial surveillance efforts have been ongoing for no more than two decades. However, mcr-1 is speculated to have originated in livestock, because colistin has been widely used in agriculture as a growth promoter since the 1970s.4Liu YY Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2016; 16: 161-168Summary Full Text Full Text PDF PubMed Scopus (2725) Google Scholar We believe large-scale retrospective studies are necessary, including not only study of the clinical source but also agricultural and environmental aspects, which might be helpful in understanding and identifying the origin of mcr-1. In April, 2017, China officially banned the use of colistin as a growth promoter in agriculture, followed by Japan, Thailand, and Canada. Evaluation of the effect of these bans on the prevalence of mcr-1 is urgent not only for agriculture, but also clinically, because the mean proportion of of mcr-1-positive isolates was 15% in humans, much higher than the previous estimate in China.2Wang Y Tian GB Zhang R et al.Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study.Lancet Infect Dis. 2017; 17: 390-399Summary Full Text Full Text PDF PubMed Scopus (198) Google Scholar According to the data from Chinese Institute of Veterinary Drug Control, the consumption of colistin has substantially reduced because of the country's ban, and initial analyses suggested the prevalence of mcr-1 in livestock has also decreased. The prevalence of mcr-1 has likely fallen in healthy individuals and clinical patients, but further epidemiological studies are needed to reveal such a trend.5Sun J Zhang H Liu YH et al.Towards understanding MCR-like colistin resistance.Trends Microbiol. 2018; 26: 794-808Summary Full Text Full Text PDF PubMed Scopus (216) Google Scholar, 8Shen Y Zhou H Xu J et al.Anthropogenic and environmental factors associated with high incidence of mcr-1 carriage in humans across China.Nat Microbiol. 2018; 3: 1054-1062Crossref PubMed Scopus (68) Google Scholar Furthermore, the surveillance of mcr-1 should be continued to fully evaluate the effects of the colistin ban not only in agriculture, but also in food processes and the supply chain.8Shen Y Zhou H Xu J et al.Anthropogenic and environmental factors associated with high incidence of mcr-1 carriage in humans across China.Nat Microbiol. 2018; 3: 1054-1062Crossref PubMed Scopus (68) Google Scholar Jiang and colleagues' study1Jiang Y Zhang Y Lu J et al.Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China: a multi-centre case-control and molecular epidemiological study.Lancet Microbe. 2020; 1: e24-e33Summary Full Text Full Text PDF Scopus (8) Google Scholar suggested that mcr-1-mediated resistance might have been overestimated on the basis of low mortality, fewer outbreaks, reduced mobility of the mcr-1 gene, and reduced cross-resistance. However, this finding is not consistent with other studies. The coexistence of blaNDM and mcr-1 has been increasing, indicating that mcr-1-positive carbapenem-resistant E coli strains have been rapidly selected as a result of increased colistin use after its approval for clinical treatment, and so has the resistance level based on the phenotypic data.9Huang H Dong N Shu L et al.Colistin-resistance gene mcr in clinical carbapenem-resistant Enterobacteriaceae strains in China, 2014–2019.Emerg Microbes Infect. 2020; 9: 237-245Crossref PubMed Scopus (16) Google Scholar The emergence of mcr-1-positive carbapenem-resistant E coli colonisation has been observed not only in hospitalised patients, but also in healthy individuals.10Shen Z Hu Y Sun Q et al.Emerging carriage of NDM-5 and MCR-1 in Escherichia coli from healthy people in multiple regions in China: a cross sectional observational study.EClinicalMedicine. 2018; 6: 11-20Summary Full Text Full Text PDF PubMed Scopus (33) Google Scholar This observation suggests that multidrug-resistant E coli and other Enterobacterales with colistin resistance might a pose severe threat to human health, and routine screening of mcr-1-positive carbapenem-resistant E coli should be considered before the admission of patients. In summary, evidence supports close monitoring of the prevalence of transmission of mcr-1, especially the potential for infection by multidrug-resistant mcr-1 positive E coli in clinical settings. Colistin could still have a substantial role in the treatment of multidrug-resistant Enterobacterales; however, surveillance of the spread of mcr-1 in healthy individuals and patients is highly encouraged. We declare no competing interests. Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China: a multicentre case-control and molecular epidemiological studyThe prevalence of mcr-1-positive E coli infection among patients increased over the study period, although it remained low. Health-care contact was the most probable risk factor. Plasmids are likely to have played a critical role in mcr-1 transmission, rather than clone dissemination and lateral transfer of IS Apl1. Our findings underscore the importance of continued surveillance of E coli strains positive for mcr-1 and potentially other resistance-associated genes, particularly in hospital settings. Full-Text PDF Open Access

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