Superbugs breach final antibiotic line of defence

E.coli strain showing resistance to colistin isolated from intensively farmed pig in China

Superbugs thought to have spread from animals have smashed through the last line in antibiotic defences and now pose a global threat, scientists say.

Researchers identified a gene that makes infectious bacteria such as Escherichia coli (E.coli) highly resistant to polymyxins, the last group of antibiotics left after all others have failed.

The discovery in China, described as "extremely worrying" by one scientist, suggests the gene can easily be transferred to bacteria with the potential to cause epidemics.

Besides E. coli they include the pneumonia bug Klebsiella pneumoniae and Pseudomonas aeruginosa, which can trigger serious lung, blood and surgical infections.

An E.coli strain showing resistance to the polymyxin drug colistin was isolated from an intensively farmed pig in Shanghai during routine testing.

Scientists found the bug was able to transfer its immunity to the drug to other strains via the mobile gene mcr-1. This led to further tests of bacterial samples collected from pigs at slaughter in four Chinese provinces, and pork and chicken sold in 30 open markets and 27 supermarkets across Guangzhou province between 2011 and 2014.

Bacteria from infected patients at two hospitals in Guangdong and Zhejiang provinces were also tested.

A high prevalence of the resistance gene was found in E. coli bugs isolated from animals and raw meat samples. The gene was also identified in 16 E.coli and K. pneumoniae samples taken from 1,322 hospitalised patients.

Alarmingly, the proportion of samples testing positive for the super-resistance gene increased from year to year, said the scientists.

Lead researcher Professor Jian-Hua Liu, from the South China Agricultural University in Guangzhou, said: “These are extremely worrying results. The polymyxins (colistin and polymyxin B) were the last class of antibiotics in which resistance was incapable of spreading from cell to cell. Until now, colistin resistance resulted from chromosomal mutations, making the resistance mechanism unstable and incapable of spreading to other bacteria.

“Our results reveal the emergence of the first polymyxin resistance gene that is readily passed between common bacteria such as Escherichia coli and Klesbsiella pneumoniae, suggesting that the progression from extensive drug resistance to pan-drug resistance is inevitable.”

It was likely that polymyxin resistance via mcr-1 originated in animals before spreading to humans, said the scientists writing in The Lancet Infectious Diseases journal.

Increasingly heavy use of colistin by Chinese farmers may have helped E.coli to acquire the gene, they added.

Worldwide, the demand for colistin in agriculture was expected to reach almost 12,000 tonnes per year by the end of this year, rising to 16,500 tonnes by 2021.

The scientists wrote: “The emergence of mcr-1 heralds the breach of the last group of antibiotics. Although currently confined to China, mcr-1 is likely to emulate other resistance genes... and spread worldwide. There is a critical need to re-evaluate the use of polymyxins in animals and for very close international monitoring and surveillance of mcr-1 in human and veterinary medicine.”

The Chinese Ministry of Agriculture has launched an immediate risk assessment of colistin use in animal feed additives.

British experts called the discovery “disturbing” and “alarming”.

Dr David Burch, veterinary surgeon and an independent member of the Ruma (Responsible Use of Medicines in Agriculture) Alliance, said: "The report of a new resistance gene (mcr-1) against polymixins (colistin) found in Escherichia coli from pigs in China, which can be potentially plasmid transferred between bacterial species and potentially to man via meat, is indeed disturbing and disappointing."

He pointed out that China’s pig farming industry is the largest in the world, more than twice the size of Europe’s. The use of generic antimicrobial drugs in animals is not normally under veterinary control in China.

The risk of the resistance gene spreading was heightened by increased trade and tourism bridging China and the West, said Dr Burch.

Professor Nigel Brown, president of the Microbiology Society, said: "This discovery that resistance to colistin can be transferred between bacteria is alarming.

“Although resistance to this important and widely-used polymyxin group of antibiotics has previously been shown, it was generally caused by mutation in individual organisms. Now that it has been demonstrated that resistance can be transferred between bacteria and across bacterial species, another line of defence against infection is in danger of being breached.

“We need careful surveillance to track the potential global spread of this resistance, and investment in research to discover new drugs with different modes of action.”


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