A new gene that makes bacteria resistant to polymyxins – the last-resort antibiotics for treating infections – is widespread in a large family of bacteria sampled from pigs and people in South China, says a new study published in The Lancet Infectious Diseases.
The researchers say some of the bacterial strains that have acquired the new resistance gene – called MCR-1 – also have epidemic potential.
The discovery is particularly alarming because the researchers found the new gene on plasmids – a mobile form of DNA that is easily shared and spread among different bacteria via horizontal gene transfer.
It echoes an earlier discovery in India a few years ago of the resistance gene NDM-1 that makes bacteria resistant to nearly all antibiotics, including the last-resort antibiotics carbapenems.
In their study, the researchers, led by members from South China Agricultural University, Guangzhou, conclude:
“The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1.”
Co-author Jian-Hua Liu, a professor specializing in antimicrobial resistance in animals, says the results are “extremely worrying” because the polymyxins were “the last class of antibiotics in which resistance was incapable of spreading from cell to cell.”
Polymyxin resistance has been known to spread via chromosomal mutations but had never been reported via horizontal gene transfer before. When it was confined to chromosomal mutations, the resistance mechanism was “unstable and incapable of spreading to other bacteria,” Prof. Liu explains.
The team found evidence that the gene passes readily between common bacteria such as Escherichia coli that cause many types of infection such as of the urinary tract, and Klebsiella pneumoniae that cause pneumonia and other infections.
Prof. Liu says this suggests “progression from extensive drug resistance to pandrug resistance is inevitable.”
The study began when the team found evidence of transferable resistance to the polymyxin drug colistin in a strain of E. coli isolated from a pig on an intensive farm in Shanghai. They discovered the resistance could be transferred to another strain.
The researchers then analyzed bacteria collected from pigs at slaughter houses and from raw pork and chicken sold across Guangzhou between 2011-14. They also analyzed samples from patients at two hospitals in Guangdong and Zhejiang provinces.
They found the MCR-1 gene was present in 166 of 804 samples of E. coli from animals and 78 of 523 samples from raw meat. They also found it in 16 samples of E. coli and K. pneumoniae taken from 1,322 hospital patients.
The team was particularly concerned by the high rate at which the MCR-1 gene copies and transfers among E. coli strains and that the proportion of positive samples increased from year to year.
The researchers suggest in their paper that “it is likely that MCR-1-mediated colistin resistance originated in animals and subsequently spread to people.”
The team also found that the gene is capable of spreading into other bacteria with epidemic potential, including Pseudomonas aeruginosa, which can cause serious infections in hospitalized patients and people with weakened immune systems.
China is a heavy user and producer of colistin and the main driver of rising global demand for the antibiotic, which is expected to exceed 13,000 tons per annum by the end of 2015 and rise at a rate of 4·75% per year.
The Chinese government has launched a risk assessment on the use of colistin in animal feed and is working with some of the team to assess the impact of MCR-1.
However, the authors note that China is not the only user of colistin in farming. Many other countries, including some in Europe, also use polymixins in agriculture, so the responsibility to accept and tackle the problem is a global one.
In an accompanying commentary, David Paterson and Patrick Harris, from the University of Queensland in Brisbane, Australia, say that the link between farm use of colistin and the presence of resistance in animals, food and human beings is now complete. One way to break the link, they note, is to limit or stop using the antibiotic in agriculture, and:
“This will require substantial political will and we call upon Chinese leaders to act rapidly and decisively. Failure to do so will create a public health problem of major dimensions.”
In a Spotlight feature on the growing problem of antibiotic resistance, Medical News Today discusses how it has become a global threat to public health that is propelling us toward a “post-antibiotic era.”