Gert van der Hoek
In Memoriam - Editor, Senior Moderator
Dissemination of the mcr-1 colistin resistance gene
Published Online:17 December 2015
Plasmid-mediated transferable colistin resistance encoded by the mcr-1 gene was described inEscherichia coli and Klebsiella pneumoniae isolates from pigs and chicken at a prevalence of around 20%, and in clinical isolates from human beings at a prevalence of around 1% in China.1 The prevalence of the mcr-1 gene in Enterobacteriaceae in other countries and in the community is unknown.
We did a prospective study of acquisition of fecal colonisation and carriage with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in 2001 Dutch travellers (the COMBAT study),2from November, 2012, to November, 2013. Acquisition was defined as the absence of ESBL-producing Enterobacteriaceae in a fecal swab sample taken immediately before travel and detection of ESBL-producing Enterobacteriaceae in a sample taken within 1?2 weeks after return to the Netherlands. Of 1847 travellers at risk, 633 (34%) acquired ESBL-producing Enterobacteriaceae. Nine of these 633 travellers acquired ESBL-producing Escherichia coli with a colistin minimum inhibitory concentration of 4?8 mg/L (EUCAST clinical breakpoint for resistance >2 mg/L) as detected using Vitek-2 and confirmed by E-test.
After publication of the report by Yi-Yun Liu and colleagues,1 these nine isolates were tested by PCR1 for the presence of the mcr-1 gene. The gene was detected in six of nine isolates and sequencing of the amplicons showed a 100% homology over the length of the fragments with the published sequence.1 Three ESBL-producing E coli were mcr-1 PCR negative, suggesting colistin resistance due to other mechanisms.3 Analysis of ESBL genes by microarray,4PCR, and sequencing showed that the mcr-1 positive ESBL-producing E coli carried ESBL genes belonging to multiple groups (table).
Of the six travellers who acquired ESBL-producing E coli carrying the mcr-1 gene, two unrelated travellers visited Peru and Bolivia, two unrelated travellers visited China, one visited Tunisia, and one visited multiple countries in southeast Asia (Thailand, Vietnam, Laos, and Cambodia). The duration of travel ranged between 8 and 40 days (mean 21?3 days). None of the travellers had accessed medical care and none had used antimicrobial drugs during travel, while five had experienced traveller's diarrhoea. Analysis of subsequent fecal samples collected at 1, 3, 6, and 12 months after return to the Netherlands did not show ESBL-producing E coli, suggesting short-term colonisation with colistin resistant ESBL-producing E coli or loss of plasmids carrying ESBL and potentially mcr-1 genes.
Colistin is used as an ultimate refuge antimicrobial drug in the treatment of infections caused by multidrug resistant Gram-negative microorganisms.5 Our data suggest a worrisome spread of the mcr-1 gene in E coli in the community across at least three continents. The diversity of ESBL genes present in mcr-1 positive isolates suggests that the mcr-1 gene might be carried on multiple plasmid backbones.
Published Online:17 December 2015
Plasmid-mediated transferable colistin resistance encoded by the mcr-1 gene was described inEscherichia coli and Klebsiella pneumoniae isolates from pigs and chicken at a prevalence of around 20%, and in clinical isolates from human beings at a prevalence of around 1% in China.1 The prevalence of the mcr-1 gene in Enterobacteriaceae in other countries and in the community is unknown.
We did a prospective study of acquisition of fecal colonisation and carriage with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in 2001 Dutch travellers (the COMBAT study),2from November, 2012, to November, 2013. Acquisition was defined as the absence of ESBL-producing Enterobacteriaceae in a fecal swab sample taken immediately before travel and detection of ESBL-producing Enterobacteriaceae in a sample taken within 1?2 weeks after return to the Netherlands. Of 1847 travellers at risk, 633 (34%) acquired ESBL-producing Enterobacteriaceae. Nine of these 633 travellers acquired ESBL-producing Escherichia coli with a colistin minimum inhibitory concentration of 4?8 mg/L (EUCAST clinical breakpoint for resistance >2 mg/L) as detected using Vitek-2 and confirmed by E-test.
After publication of the report by Yi-Yun Liu and colleagues,1 these nine isolates were tested by PCR1 for the presence of the mcr-1 gene. The gene was detected in six of nine isolates and sequencing of the amplicons showed a 100% homology over the length of the fragments with the published sequence.1 Three ESBL-producing E coli were mcr-1 PCR negative, suggesting colistin resistance due to other mechanisms.3 Analysis of ESBL genes by microarray,4PCR, and sequencing showed that the mcr-1 positive ESBL-producing E coli carried ESBL genes belonging to multiple groups (table).
Of the six travellers who acquired ESBL-producing E coli carrying the mcr-1 gene, two unrelated travellers visited Peru and Bolivia, two unrelated travellers visited China, one visited Tunisia, and one visited multiple countries in southeast Asia (Thailand, Vietnam, Laos, and Cambodia). The duration of travel ranged between 8 and 40 days (mean 21?3 days). None of the travellers had accessed medical care and none had used antimicrobial drugs during travel, while five had experienced traveller's diarrhoea. Analysis of subsequent fecal samples collected at 1, 3, 6, and 12 months after return to the Netherlands did not show ESBL-producing E coli, suggesting short-term colonisation with colistin resistant ESBL-producing E coli or loss of plasmids carrying ESBL and potentially mcr-1 genes.
Colistin is used as an ultimate refuge antimicrobial drug in the treatment of infections caused by multidrug resistant Gram-negative microorganisms.5 Our data suggest a worrisome spread of the mcr-1 gene in E coli in the community across at least three continents. The diversity of ESBL genes present in mcr-1 positive isolates suggests that the mcr-1 gene might be carried on multiple plasmid backbones.