Plasmid-mediated colistin resistance

The recently discovered colistin resistance-encoding element, mcr-1, adds to the list of mobile resistance genes whose products rapidly erode the antimicrobial efficacy of not only the commonly used antibiotics, but also the last line agents of carbapenems and colistin. The relative prevalence of mcr-1-bearing strains in various ecological niches including 1,371 food samples, 480 animal faecal samples, 150 human faecal samples and 34 water samples was surveyed using a novel in-house method. Bacteria bearing mcr-1 were commonly detected in water (71% of samples), animal faeces (51%), food products (36%), and exhibited stable carriage in 28% of human subjects surveyed. Such strains, which exhibited variable antibiotic susceptibility profiles, belonged to various Enterobacteriaceae species, with Escherichia coli being the most dominant in each specimen type. The mcr-1 gene was detectable in the chromosome as well as plasmids of various sizes. Among these, two conjugative plasmids of sizes ca 33 and ca 60 kb were found to be the key vectors that mediated mcr-1 transmission in organisms residing in various ecological niches. The high mcr-1 carriage rate in humans found in this study highlights the importance of continued vigilance, careful antibiotic stewardship, and the development of new antimicrobials.

Colistin resistance genes mcr-3 and mcr-1 have been detected in an Escherichia coli isolate from cattle faeces in a Spanish slaughterhouse in 2015. The sequences of both genes hybridised to same plasmid band of ca 250 kb, although colistin resistance was non-mobilisable. The isolate was producing extended-spectrum beta-lactamases and belonged to serotype O9:H10 and sequence type ST533. Here we report an mcr-3 gene detected in Europe following earlier reports from Asia and the United States.

A novel mcr colistin resistance gene was identified in a strain of Salmonella enterica, monophasic variant of serovar Typhimurium (4,5,12:i:- ), isolated from a pig at slaughter in Italy in 2013, and in Escherichia coli strains collected during routine diagnostic of post-weaning diarrhoea in pigs from Spain and Belgium in 2015 and 2016. Immediate implementation of mcr-screening including this novel gene variant is required for Salmonella and E. coli from humans and food-producing animals in Europe.

We describe three cases of bloodstream infection caused by colistin-resistant Escherichia coli in patients in a tertiary hospital in Italy, between August 2016 and January 2017. Whole genome sequencing detected the mcr-1 gene in three isolated strains belonging to different sequence types (STs). This occurrence of three cases with mcr-1-positive E. coli belonging to different STs in six months suggests a widespread problem in settings where high multidrug resistance is endemic such as in Italy.

The mcr-1 gene was found in 11 isolates from a Portuguese Salmonella collection (n = 1,010; 58 serotypes; 2002–15) of clinical samples, foodstuff, food-animals and water. Mcr-1 has been located on different plasmids (IncX4/IncHI2) in pig-associated multidrug-resistant, copper-tolerant S.1,4,[5],12:i:-/ST34 and S. Rissen/ST469 clones from human and pork products since at least 2011. Our data highlight dissemination of mcr-1 by successful resistant clones in Europe and raise questions about the efficacy of copper-based interventions to reduce colistin use.

Colistin resistance was detected in 53 of 10,011 Escherichia coli (0.5%) by prospective phenotypic testing of consecutive clinical isolates in a single hospital in Barcelona, Spain (2012–15). The mcr-1 gene was retrospectively identified by PCR and sequencing in 15 of 50 available isolates. Each isolate had a unique PFGE pattern except for two. This clonal diversity supports the hypothesis of horizontal dissemination of the mcr-1 gene in the local study population.

Recently, the plasmid-mediated colistin resistance gene mcr-1 was found in Enterobacteriaceae from humans, pigs and retail meat in China. Several reports have documented global presence of the gene in Enterobacteriaceae from humans, food animals and food since. We screened several well-characterised strain collections of Enterobacteriaceae, obtained from retail chicken meat and hospitalised patients in the Netherlands between 2009 and 2015, for presence of colistin resistance and the mcr-1 gene. A total of 2,471 Enterobacteriaceae isolates, from surveys in retail chicken meat (196 isolates), prevalence surveys in hospitalised patients (1,247 isolates), clinical cultures (813 isolates) and outbreaks in healthcare settings (215 isolates), were analysed. The mcr-1 gene was identified in three (1.5%) of 196 extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates from retail chicken meat samples in 2009 and 2014. Two isolates were obtained from the same batch of meat samples, most likely representing contamination from a common source. No mcr-1-positive isolates were identified among 2,275 human isolates tested. All mcr-1-positive isolates were colistin-resistant (minimum inhibitory concentration (MIC) > 2 mg/L). Our findings indicate that mcr-1-based colistin-resistance currently poses no threat to healthcare in the Netherlands. They indicate however that continued monitoring of colistin resistance and its underlying mechanisms in humans, livestock and food is needed.

Colistin resistance was investigated in 1,696 isolates collected from 2007 to 2014 within the frame of the French livestock antimicrobial resistance surveillance programme. The mcr-1 gene was detected in all commensal Escherichia coli isolates with a minimum inhibitory concentration to colistin above the 2 mg/L cut-off value (n=23). In poultry, mcr-1 prevalence was 5.9% in turkeys and 1.8% in broilers in 2014. In pigs, investigated in 2013, this prevalence did not exceed 0.5%. These findings support that mcr-1 has spread in French livestock.