A number of people in China might be infected with bacteria resistant to an antibiotic used as a last resort, two new studies suggest.

The mcr-1 gene, a gene that enables bacterial resistance to colistin, an antibiotic of last resort, has been found in a wide variety of strains of Escherichia coli in China after it’s large scale use of colistin in agriculture. The gene is transferable between different bacteria.

Infections that are resistant to carbapenems are already common in many countries and in these cases only a small number of antibiotics are effective, including colistin. In 2015, the mcr-1 gene was detected in China in E.coli in pigs as a result of overuse.

Subsequently, the gene was identified in other countries including Denmark, Germany, Vietnam, Spain, and the USA among others, raising fears that bacteria may acquire combined colistin and carbapenem resistance, making them multi-drug resistant.

Significant Risk Factors

China is now preparing to introduce colistin for the first time in human medicine. The two new studies give evidence of how far the mcr-1 gene has spread to bacteria in clinical settings. The affected bacteria includes a minority already resistant to the carbapenem class of antibiotics.

Professor Tim Walsh, who co-led the first study, says:

“The emergence of mcr-1 heralds the breach of the last group of antibiotics, such as colistin. The withdrawal of the drug from agricultural use, and its introduction in the clinic might reduce colistin resistance rates in the community, and increase resistance in hospitals where they may be harder to treat or spread more easily. Our study finds that there are significant risk factors for the spread of mcr-1 infections, beyond just rural living and diet. The spread of colistin resistant bacteria will likely worsen when the drug is introduced in humans."

The study, led by Professor Timothy Walsh at Cardiff University (UK) and Professor Jianzhong Shen at the China Agricultural University, investigated the prevalence of bacteria carrying the mcr-1 resistance gene in human infections in two hospitals in Zheijang and Guangdong provinces across 8 years. Among more than 17000 bacterial isolates associated with infection, mcr-1 was detected in 76/5332 samples of E coli and 13/348 samples of Klebsiella pneumoniae.

The study is the first to look at risk factors for clinical mcr-1 infection and found that people who had used antibiotics (particularly carbapenems) before hospitalisation were more likely to carry bacteria with the mcr-1 resistance gene. Among 146 isolates of mcr-1-positive E coli identified, only five were also carbapenem resistant.

MCR-1 Gene Positive

The second study was led by researchers at Zhejiang University. Samples from over 2000 bloodstream infections at 28 hospitals in China were tested.

Of the 1495 E coli samples, 20 were mcr-1 positive, one of which was also carbapenem resistant. Patients with mcr-1-positive infections were all treated successfully with other antibiotics.

“The most troubling problem for clinicians would be the transfer of colistin resistance to a bacterium which is already carbapenem resistant, making it multi-drug resistance. This does not appear to have happened to any great extent in clinical isolates, but the situation should be monitored carefully as the country prepares to introduce colistin for use in humans,"

says Professor Yunsong Yu, Zhejiang University.

Currently categorised by the FDA as a dangerous drug, colistin is available in oral dosage and injection form. Colistin, also known as polymyxin E, is an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. It is effective against most Gram-negative bacilli.

Colistin-resistant E. coli was identified in the United States in May 2016.

Jingjing Quan, MS , Xi Li, PhD , Yan Chen, PhD , Yan Jiang, PhD , Zhihui Zhou, PhD , Huichuan Zhang, MS , Lu Sun, MS , Zhi Ruan, PhD , Ye Feng, PhD , Murat Akova, MD , Prof Yunsong Yu, MD Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study The Lancet Infectious Diseases DOI: http://dx.doi.org/10.1016/S1473-3099(16)30528-X

Yi-Yun Liu, BS, Yang Wang, PhD, Prof Timothy R Walsh, DSc , Ling-Xian Yi, BS , Rong Zhang, PhD , James Spencer, PhD , Yohei Doi, MD , Guobao Tian, PhD , Baolei Dong, BS , Xianhui Huang, PhD , Lin-Feng Yu, BS, Danxia Gu, Ph , Hongwei Ren, BS, Xiaojie Chen, MS, Luchao Lv, MS , Dandan He, MS , Hongwei Zhou, PhD , Prof Zisen Liang, MS , Prof Jian-Hua Liu, PhDc, Prof Jianzhong Shen, PhD Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study The Lancet Infectious Diseases, Volume 16 , Issue 2 , 161 - 168

Image: National Institute of Allergy and Infectious Diseases, National Institutes of Health

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