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Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant EnterobacteriaceaeIn The Lancet Infectious Diseases, Yi-Yun Liu and colleagues1 described mcr-1—a plasmid-mediated gene that confers colistin resistance in Escherichia coli and Klebsiella pneumoniae isolates cultured from animals and patients in China. Following this initial finding, several reports2, 3, 4, 5, 6 showed that mcr-1 has spread beyond China into south Asia, Europe, Africa, and South America, and into other Enterobacteriaceae species. These reports confirm the finding that the mcr-1 gene is mobilised on plasmids that have spread to different Enterobacteriaceae. Of clinical concern is the inevitable spread of a plasmid harbouring the mcr-1 gene into a carbapenem-resistant Enterobacteriaceae, creating a multidrug-resistant isolate that approaches pandrug resistance. Liu and colleagues' study1 raised concern that mcr-1-mediated resistance was spreading in our local hospital settings. In response to this potential clinical problem, we retrospectively genotyped 17 colistin-resistant (European Committee on Antimicrobial Susceptibility Testing clinical breakpoint for resistance >2 μg/mL) Enterobacteriaceae isolates, including nine Salmonella spp, two Pantoea agglomerans, two E coli, and four K pneumoniae, collected between January, 2013, and November, 2015, from a tertiary hospital in Suzhou, China, for the presence of the mcr-1 gene by use of a previously described PCR assay.1 The mcr-1 gene was detected in four isolates (two E coli and two K pneumoniae; table), and sequencing of the PCR amplicons confirmed they all carry mcr-1. Table Characteristics of mcr-1-harbouring isolates
ESBL=extended-spectrum β-lactamase.
[size=0.9em]*Determined by MicroScan WalkAway plus System.
The four isolates were obtained from different sources (blood, surgery wound, and drainage fluid) in three patients: one inpatient in 2014, and one inpatient and one outpatient in 2015. Most striking, and of great global public health concern, is that the antibiotic susceptibility results showed that the twoK pneumoniae isolates were non-susceptible to nearly all antimicrobial drugs tested, including imipenem and meropenem (table). Additional PCR and sequencing analysis for the carbapenemase genes showed that the two K pneumoniae isolates carry the gene for NDM-5, a variant that has increased carbapenemase activity by comparison with NDM-1. Carbapenem and colistin resistance were successfully transferred to E coli DH5α strains via electroporation individually, suggesting that the mcr-1 and blaNDM-5 genes are located on different transferable plasmids. Complete sequencing ofmcr-1-harbouring and blaNDM-5-harbouring plasmids, and whole genome sequencing, are underway. Our retrospective study documents that the mcr-1 gene has already established itself in highly drug-resistant Enterobacteriaceae species, including its movement into carbapenem-resistant strains carrying an NDM-5 resistance plasmid. The coexistence of MCR-1 resistance and the NDM-5 approaches a pandrug-resistant phenotype for which the use of colistin and the new β-lactam–β-lactamase inhibitor, ceftazidime–avibactam, is ineffective. These findings stress the need to monitor the use of colistin in treatment of both human beings and animals, and the need for active surveillance to identify colistin resistance and for heightened infection control practices to restrict its further dissemination. This study was supported by grants from the National Institutes of Health ( grant R01AI090155 ) and National Natural Science Foundation of China ( number 81572032 ). We declare no competing interests. LC, YWT, and BNK conceived and designed the experiments. HD collected data and did the experiments. HD and LC analysed the data. LC, YWT, and BNK wrote the report. All authors reviewed and approved the final report.
References
- Liu, Y-Y, 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: 161–168
- Hasman, H, Hammerum, AM, Hansen, F et al. Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. Euro Surveill. 2015; 20: 30085
- Arcilla, MS, van Hattem, JM, Matamoros, S et al. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis. 2016; 16: 147–149
- Olaitan, AO, Chabou, S, Okdah, L, Morand, S, and Rolain, J-M. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis. 2016; 16: 147
- Webb, HE, Granier, SA, Marault, M et al. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis. 2016; 16: 144–145
- Tse, H and Yuen, K-Y. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis. 2016;16: 144–145
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发表于 2016-6-15 16:32:18
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发表于 2016-6-15 17:44:21
