Abstract
Colistin is used as an alternative therapeutic for carbapenemase-producing Enterobacteriaceae (CPE) infections which are spreading at a very high rate due to the transfer of carbapenemase genes through mobile genetic elements. Due to the emergence of mcr-1, the plasmid-mediated colistin resistance gene, mcr-1-positive Enterobacteriaceae (MCRPEn) pose a high risk for the transfer of mcr-1-carrying plasmid to CPE, leading to a situation with no treatment alternatives for infections caused by Enterobacteriaceae possessing both mcr-1 and carbapenemase genes. Here, we report the application of PCR-dipstick-oriented surveillance strategy to control MCRPEn and CPE by conducting the PCR-dipstick technique for the detection of MCRPEn and CPE in a tertiary care hospital in Thailand and comparing its efficacy with conventional surveillance method. Our surveillance results showed a high MCRPEn (5.9%) and CPE (8.7%) carriage rate among the 219 rectal swab specimens examined. Three different CPE clones were determined by pulsed-field gel electrophoresis (PFGE) whereas only two MCRPEn isolates were found to be closely related as shown by single nucleotide polymorphism-based phylogenetic analysis. Whole genome sequencing (WGS) and plasmid analysis showed that MCRPEn carried mcr-1 in two plasmids types—IncX4 and IncI2 with ~99% identity to the previously reported mcr-1-carrying plasmids. The identification of both MCRPEn and CPE in the same specimen indicates the plausibility of plasmid-mediated transfer of mcr-1 genes leading to the emergence of colistin- and carbapenem-resistant Enterobacteriaceae. The rapidity (<2 h) and robust sensitivity (100%)/specificity (~99%) of PCR-dipstick show that this specimen-direct screening method could aid in implementing infection control measures at the earliest to control the dissemination of MCRPEn and CPE.
Highlights
Since carbapenems are regarded as the last line of defense for several multidrug-resistant bacterial infections, carbapenemresistant organisms impede the effective treatment options and increase the mortality rate of afflicted patients (Kizny Gordon et al, 2017)
Since multidrug-resistant carbapenemase-producing Enterobacteriaceae (CPE) are well-known for their acquisition of plasmid carrying carbapenemase genes, it is suspected that they could acquire the mcr-1-carrying plasmid from mcr-1-producing Enterobacteriaceae (MCRPEn) which might lead to the emergence of the superbug resistant to both colistin and carbapenem without alternate treatment regimens
Two MCRPEnpositive specimens carried both E. coli and K. pneumoniae with mcr-1 gene and we found 15 MCRPEn isolates from 13 MCRPEn-positive specimens
Summary
Since carbapenems are regarded as the last line of defense for several multidrug-resistant bacterial infections, carbapenemresistant organisms impede the effective treatment options and increase the mortality rate of afflicted patients (Kizny Gordon et al, 2017). Amongst different carbapenem-resistant organisms, carbapenemase-producing Enterobacteriaceae (CPE) are posing a global health threat due to their hasty dissemination, enabled through the horizontal transfer of carbapenemase genes (van Duin and Doi, 2017). Several Enterobacteriaceae species are known to be intrinsically resistant to colistin, after the description of mcr-1, the plasmid-encoded colistin resistance gene, mcr-1-producing Enterobacteriaceae (MCRPEn) have been reported worldwide (Olaitan et al, 2014; Liu et al, 2016; Matamoros et al, 2017; Wang et al, 2018). Since multidrug-resistant CPE are well-known for their acquisition of plasmid carrying carbapenemase genes, it is suspected that they could acquire the mcr-1-carrying plasmid from MCRPEn which might lead to the emergence of the superbug resistant to both colistin and carbapenem without alternate treatment regimens. Recent reports show the sporadic identification of Enterobacteriaceae co-harboring carbapenemase and mcr-1 in plasmids (Beyrouthy et al, 2017; Pulss et al, 2017; Mendes et al, 2018)
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