Abstract
BackgroundColistin is a last resort antibiotic for the treatment of carbapenem-resistant Gram negative infections. Until recently, mechanisms of colistin resistance were limited to chromosomal mutations which confer a high fitness cost and cannot be transferred between organisms. However, a novel plasmid-mediated colistin resistance mechanism, encoded by the mcr-1 gene, has been identified, and has since been detected worldwide. The mcr-1 colistin resistance mechanism is a major threat due to its lack of fitness cost and ability to be transferred between strains and species. Surveillance of colistin resistance mechanisms is critical to monitor the development and spread of resistance.This study aimed to determine the prevalence of the plasmid-mediated colistin resistance gene, mcr-1, in colistin-resistant E. coli and Klebsiella spp. isolates in the Western Cape of South Africa; and whether colistin resistance is spread through clonal expansion or by acquisition of resistance by diverse strains.MethodsColistin resistant E. coli and Klebsiella spp. isolates were collected from the NHLS microbiology laboratory at Tygerberg Hospital. Species identification and antibiotic susceptibility testing was done using the API® 20 E system and the Vitek® 2 Advanced Expert System™. PCR was used to detect the plasmid-mediated mcr-1 colistin resistance gene and REP-PCR was used for strain typing of the isolates.ResultsNineteen colistin resistant isolates, including 12 E. coli, six K. pneumoniae and one K. oxytoca isolate, were detected over 7 months from eight different hospitals in the Western Cape region. The mcr-1 gene was detected in 83% of isolates which were shown to be predominantly unrelated strains.ConclusionsThe plasmid-mediated mcr-1 colistin resistance gene is responsible for the majority of colistin resistance in clinical isolates of E. coli and Klebsiella spp. from the Western Cape of South Africa. Colistin resistance is not clonally disseminated; the mcr-1 gene has been acquired by several unrelated strains of E. coli and K. pneumoniae. Acquisition of mcr-1 by cephalosporin- and carbapenem-resistant Gram negative bacteria may result in untreatable infections and increased mortality. Measures need to be implemented to control the use of colistin in health care facilities and in agriculture to retain its antimicrobial efficacy.
Highlights
Colistin is a last resort antibiotic for the treatment of carbapenem-resistant Gram negative infections
In November 2015, the emergence of a novel plasmid-mediated colistin resistance mechanism was described [7]. This colistin resistance is conferred by the mcr-1 gene which was identified on an IncI2 plasmid, pHNSHP45, isolated from an Escherichia coli isolate from a pig in China
This study aimed to determine the prevalence of the plasmid-mediated colistin resistance gene, mcr-1, in colistin-resistant E. coli and Klebsiella spp. isolates in the Western Cape of South Africa; and to determine whether colistin resistance is spread through clonal expansion or by acquisition of resistance by diverse strains
Summary
Colistin is a last resort antibiotic for the treatment of carbapenem-resistant Gram negative infections. A novel plasmid-mediated colistin resistance mechanism, encoded by the mcr-1 gene, has been identified, and has since been detected worldwide. Colistin resistance was considered to be due to rare chromosomal mutations in the genes encoding the PmrA/PmrB and PhoP/PhoQ two component signalling systems or the negative regulator MgrB [6]. These mutations result in modifications to the Lipid A molecule, or rarely, the complete loss of Lipid A. These chromosomal mutations confer a fitness cost to the organism and are unlikely to be maintained in the absence of colistin selection; and are not transferable to other organisms. Subsequent studies have identified the mcr gene in various Enterobacteriaceae, including E. coli, K. pneumoniae and Salmonella spp., in Asia, Europe, North America and Africa [8,9,10,11,12,13,14,15,16]
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