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The discovery of a gene with allows bacteria to become resistant to a specific type of antibiotic (one considered a “last line of defence”) has been reported in the Lancet Infectious Diseases journal.
Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:
“This is an important study which highlights a potential threat to the effectiveness of colistin – a useful antibiotic for treating E. coli infections. Although spontaneous resistance to the antibiotic is encountered in the clinic, that resistance compromises the pathogen’s fitness, meaning it is less able to replicate and cause infections.
“However this study reports on a new strain of E. coli, isolated from pigs in China, which has acquired a special resistance gene from another bacterium. This form of antibiotic resistance is much more stable and does not decrease the bug’s fitness. Clearly this has means that the infections will become more difficult to treat and that the pathogen will be more likely to retain the antibiotic resistance. Furthermore, there is a possibility that it will spread to other pathogenic bacteria.
“At a time when antibiotic resistance is increasing across the globe, this form of resistance is one we have to study closely and learn from quickly.”
Dr David Burch, veterinary surgeon and independent member of the RUMA Alliance (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. Formerly, colistin resistance both in man and animals was thought to be chromosomally related and therefore unlikely to be transferred.
“It is noted that most of the genetic work was carried out on a plasmid basis and not on the resistance gene itself, so the final link between pigs, pork, man and human disease has not been completely established. Recent work looking at attribution of extended-spectrum beta lactamase resistance from food to man has shown that man to man is the major contributor (99.74%: 0.26%) (Burch, 2015) due to hospital and care facility spread of bacteria carrying the resistance genes. Further genetic work is required to confirm the direct linkage between food and man with the mcr-1 gene
“So saying, it must be remembered that China has the largest pig production in the world – over twice that of Europe’s; they are major producers of generic antimicrobial drugs and their use in animals is not normally under veterinary control. Fortunately, the supply of live pigs and pork is in the direction from Europe to China and due to the nature of the endemic diseases in China, such as Foot and Mouth Disease, it is unlikely that this will be reversed. The possibility of transfer by man, however, is a more likely risk with increased trade and tourism between the two regions of the world. This is a good example of the complexity and global nature of antibiotic resistance and the need for countries to work together to address this One Health issue.
“In the response to the European Commission by the European Medicines Agency (2013) regarding the use of old classes of antibiotics, like colistin, which have been re-introduced to treat multi-resistant bacteria in humans they recommended: “Despite the abundant use of colistin in veterinary medicine for over 50 years, from the available information colistin resistance transmission via horizontal gene transfer or sustained clonal expansion has not been observed for the target Gram-negative organisms. However the rapid emergence of resistance in humans after oral use in the Intensive Care Unit (ICU) for selective digestive tract decontamination shows that resistance in Enterobacteriaceae can emerge following oral use. The lack of emergence of resistance should be addressed with caution since in depth epidemiological surveys in veterinary medicine are scarce. Large studies combining consumption and resistance are limited, because colistin susceptibility tests are not fully reliable. There is a need to implement robust systems for surveillance of antimicrobial resistance to detect any potential increase of colistin resistance in animal bacteria in the future that could lead to a review of the current advice.”
“In Europe, 80% of polymixin (mainly colistin) sales are made in only 3 out of 26 Member States i.e. Spain, Germany and Italy (ESVAC, 2015) and it would be of great value to review the surveillance data from these countries to see if the situation has changed dramatically in recent years, before any radical decisions over restrictions of use in veterinary medicine are made here. The health and welfare of the animals treated responsibly with this medication also needs to be weighed up against any possible over-reaction before a full review has taken place.”
References:
Burch, D.G.S. (2015) Use of antibiotics in animals and people. Veterinary Record, 177, 11, 292-293.
EMA (2013) European Medicines Agency – Answer to the first request from the European Commission for scientific advice on the impact on public health and animal health of the use of antibiotics in animals. EMA/363834/2013.
ESVAC (2015) European Medicines Agency – Fifth ESVAC report – Sales of veterinary antimicrobial agents in 26 EU/EAA countries in 2013.
Prof. 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.”
Prof. Laura Piddock, Professor of Microbiology, University of Birmingham, said:
“This is a worrying report as polymyxins are often the last resort antibiotic to treat serious infections by multiple drug-resistant bacteria. However, concern must be tempered, as there is no evidence so far to show that patients with such drug-resistant infections will be difficult to treat. Nonetheless, equally worrying is that this type of resistance can be easily transferred between bacteria and as we know from other types of drug-resistance, this likely paves the way for it to spread throughout the world.
“As this week is World Antibiotic Awareness Week, the timing of publication could not be more appropriate. The finding that this type of resistance can be shared by different bacteria, irrespective of whether from food, an animal or a person is further evidence that the same drugs should not be used in veterinary and human medicine.
“All use of polymyxins must be minimised as soon as possible and all unnecessary use stopped. Now more than ever we need rapid accurate diagnostics to indicate when antibiotics should be used, so that doctors use these drugs only when really needed. Until that time global surveillance for this type of resistance is essential so that infection control measures can be put in place to prevent the spread of these polymyxin-resistant bacteria.”
‘Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study’ by Yi-Yun Liu et al. published in the Lancet Infectious Diseases on Wednesday 18 November 2015.
Declared interests
Dr Simon Clarke has no conflicts of interest to declare.
Dr David Burch is a veterinarian and specialist in pig medicine and also a consultant to the animal health industry.
Prof. Nigel Brown declares that he has no relevant interests.
Prof. Laura Piddock: For her basic research, Prof Piddock is currently in receipt of funding from the BBSRC and MRC, and has a Roche Extending the Innovation Network Award. Professor Piddock is the vice-chair of the EU Joint Programming Initiative on AMR scientific advisory board. She is also member of the Longitude Prize Advisory panel.