H5N1

Plasmid-encoded colistin resistance: mcr-1, 2, 3 and counting

Eurosurveillance this week is all about plasmid-mediated colistin resistance. It leads off with an editorial: Plasmid-encoded colistin resistance: mcr-1, 2, 3 and counting. Excerpt:

In November 2015, the first description of plasmid-mediated colistin resistance (mcr-1 gene) was reported from China in food animals, food and humans. Many reports from all over the world have followed since. The reported rates vary considerably, ranging from sporadic findings up to 67% in Escherichia coli isolates from Tunisian chicken. 

However, the rates have been consistently higher in livestock than in humans. This points to a reservoir in animals with spill over to humans. Until recently, colistin use in humans has been limited but it has been used extensively in veterinary medicine for decades, both as curative treatment and for prevention of disease. 

The amount of use in livestock varies enormously. In Europe, for example, in 2013, the annual colistin sales in some countries exceeded 20 mg per population corrected unit (PCU) while in other countries the sales were below 1 mg/PCU. 

Following the detection of mcr-1, the European Medicines Agency updated their advice on the use of colistin in humans and animals with the aim of reducing the use in animals by 65% in the coming years. Quantitative targets of 5 mg/PCU and 1 mg/PCU have been set for a reduction in high and medium consuming countries, respectively.  

In the summer of 2016, a group from Belgium reported a new variant of the plasmid-mediated colistin resistance gene, mcr-2. Xavier et al. studied colistin-resistant E. coli strains from pigs and calves and found mcr-2 more frequently than mcr-1. 

In this issue of Eurosurveillance, there are three reports on a third variant, mcr-3. In one of the studies, mcr-3 was detected in an E. coli isolate from a patient with a bloodstream infection who had recently visited Thailand.

The editorial contains a postscript about a fourth article, just squeezed in at the last minute, reporting the discovery of mcr-4.

CIDRAP: New colistin resistance gene identified in China

Via CIDRAP, a June 28 report by Chris Dall: New colistin resistance gene identified in China. Excerpt:

Researchers in China have discovered another gene that confers resistance to the last-resort antibiotic colistin. 

In a study yesterday in mBio, the researchers report that the MCR-3 gene was discovered in a fecal sample obtained from an apparently healthy pig at a farm in Shandong province during a routine surveillance study of antimicrobial resistant bacteria. The gene was located on a colistin-resistant Escherichia coli isolate, on a plasmid that contained 18 additional antibiotic resistance genes. 

The authors of the study say they're concerned the gene may already be widely disseminated, and that scientists should be on the lookout for it. "Screening for the mcr-3 gene should be urgently included in the surveillance of colistin-resistant Gram-negative pathogens from animals, humans, and the environment," they write. 

A third mobile colistin-resistance gene 

The discovery was made by several members of the research team that first reported the discovery of the mobile colistin resistance gene MCR-1 in E coli from pigs, pork products, and humans in China in November 2015. That finding raised international concern, given that colistin is an antibiotic of last resort for multidrug-resistant bacterial infections. The gene's location on plasmids, which are highly mobile pieces of DNA that can be shared within and between different bacterial species, means that resistance to colistin can quickly spread.  

Since then, MCR-1 has been identified in bacteria from humans, animals, and the environment in more than 30 countries, including the United States, and studies have documented the spread of the gene to the clinical setting in China. Earlier this year, Chinese scientists reported an outbreak of MCR-1–carrying Klebsiella pneumoniae among patients in a pediatric leukemia ward.  

In addition, six different variants of the MCR-1 gene have been reported, along with a second mobile resistance gene, MCR-2.  

Eurosurveillance: Here comes mcr-2

Via this week's Eurosurveillance: Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. The abstract:

We identified a novel plasmid-mediated colistin-resistance gene in porcine and bovine colistin-resistant Escherichia coli that did not contain mcr-1. The gene, termed mcr-2, a 1,617 bp phosphoethanolamine transferase harboured on an IncX4 plasmid, has 76.7% nucleotide identity to mcr-1. Prevalence of mcr-2 in porcine colistin-resistant E. coli (11/53) in Belgium was higher than that of mcr-1 (7/53). These data call for an immediate introduction of mcr-2 screening in ongoing molecular epidemiological surveillance of colistin-resistant Gram-negative pathogens.

STAT is already on the story with a clear explanation of this finding's very unpleasant implications.