Polymyxins remain the last line of defense against antibiotic-resistant Gram-negative bacteria. Now, researchers report that a gene that confers resistance to these drugs is found in a growing number of bacteria from meat samples in China — and from some hospital patients. More worrying is that the gene, mcr-1, is found on small pieces of DNA called plasmids that easily spread between bacteria.
"The implications of this finding are enormous," write David L Paterson, MD, from Royal Brisbane and Women's Hospital Campus in Australia, and Patrick N. A. Harris, MBBS, from Wesley Hospital, also in Brisbane, in an accompanying editorial.
The editorial and research paper, by Yi-Yun Liu, from the College of Veterinary Medicine, National Risk Assessment Laboratory for Antimicrobial Resistance of Microorganisms in Animals, South China Agricultural University, Guangzhou, China, and colleagues, were published online November 18 in the Lancet Infectious Diseases.
The researchers found that in 2011, more than 5% of Escherichia coli isolates from retail chicken and pork meat from China tested positive for the colistin (polymyxin E) resistance gene mcr-1. By November 2014, the last date for which data are available, the percentage of positive isolates had increased to approximately 25%.
Thus, not only have microbes now achieved resistance to polymyxin, but the resistance is spreading quickly. The rapid spread is a result of the fact that mcr-1 is not located on the chromosome, as has been the case for previously identified polymyxin-resistant genes, but is found on plasmids that bacteria exchange regularly.
E coli and Klebsiella pneumoniae Strains Affected
The researchers investigated the prevalence of mcr-1 in E coli and K pneumoniae strains gathered from five provinces in China between April 2011 and November 2014. They found a high prevalence of mcr-1 in E coli isolates from animals, as well as isolates from retail meat. Overall, 78 (15%) of 523 samples of raw meat carried the mcr-1 plasmid, as did E coli isolated from 166 (21%) of 804 animals.
Moreover, there was an apparent increase in the proportion of mcr-1-positive E coli during the study. In chicken, the percentage of positive samples was 4.9% in 2011, 25.0% in 2013, and 28.0% in 2014. Similar rates were found in pork samples, at 6.3% in 2011, 22.9% in 2014, and 22.3% in 2014.
To put these data in perspective, in 2014, China produced 17.5 million tonnes of poultry and 56.7 million tonnes of pork, making it the world's largest producer of both products. Approximately 10% of the meat is exported.
The researchers also report that 16 (1%) of the 1322 samples from inpatients with infection were positive for mcr-1 in 2014, the only year for which they report patient data.
The authors express concern that the resistance gene may spread beyond China. "During the writing of this report, we noted that five E. coli DNA contigs containing mcr-1-like genes from Malaysia have been recently submitted to the European Molecular Biology Laboratory.... Although no additional information is available, the possibility that mcr-1-positive E. coli have spread outside China and into other countries in southeastern Asia is deeply concerning," they write.
Polymyxin Is the Last Line of Defense
Dr Paterson and Dr Harris note in their editorial that although new antibiotics have recently come into the clinic, the drugs are not effective against all clinically important Gram-negative bacteria. "For this reason, the polymyxins (colistin and polymyxin B) remain the last line of defence against many Gram-negative bacilli," they write.
In 2012, the World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistance described colistin as an antibiotic of critical importance.
"There have been previous calls for curtailing the use of polymyxins in agriculture. We must all reiterate these appeals and take them to the highest levels of government or face increasing numbers of patients for whom we will need to say, 'Sorry, there is nothing I can do to cure your infection,' " the editorialists write.
The authors of the Chinese study echo that sentiment. "In the absence of new agents effective against resistant Gram-negative pathogens, the effect on human health by mobile colistin resistance cannot be underestimated. It is imperative that surveillance and molecular epidemiological studies on the distribution and dissemination of mcr-1 among Gram-negative bacteria in both human and veterinary medicine are initiated, along with re-evaluation of the use of polymyxins in animals."
The researchers have disclosed no relevant financial relationships. Dr Paterson has received honoraria for advisory boards from Merck, AstraZeneca, Shionogi, Meij, and GlaxoSmithKline. Dr Harris has disclosed no relevant financial relationships.
Lancet Infect Dis. Published online November 18, 2015.
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