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expert reaction to reports that the gene that enables bacteria to be resistant to polymyxins (last line of antibiotic defence such as colistin) have been detected in Denmark

It has been reported that samples of E.coli which are resistant to an antibiotic of last resort have been found in Denmark.

 

Prof. Laura Piddock, Professor of Microbiology, University of Birmingham, said:

“This is a worrying report as colistin is often the last resort antibiotic to treat serious infections by multiple drug-resistant bacteria. The finding that this new type of resistance has now been found in bacteria isolated from food and one patient in Denmark as far back as 2012 means that this type of resistance may be widespread. Indeed, this finding questions whether it originated in China.

“Bacteria are able to transfer resistance from one bacterium to another by exchanging circular pieces of DNA called plasmids that carry the colistin-resistance gene. The bacteria from Denmark were also resistant to another type of drug, meaning that the options for treatment were further reduced.

“This type of resistance can be easily transferred between bacteria and as we know from other types of drug-resistance, this means that it can easily spread throughout the world. 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. To reduce the likelihood this type of drug resistance being shared by bacteria all use of colistin must be minimised as soon as possible and all unnecessary use stopped.

“There are some antibiotics and combinations of drugs that could be used to treat infections by bacteria with the colistin-resistance plasmid, so hopefully the post-antibiotic era is not upon us yet. However, this is a wake-up call to the world to make available much more funding to find new treatments – some compounds with good activity in the test tube offer promise, but without funding to test them to ensure their safety in people and how to minimize resistance emergence, problems with difficult or untreatable infections will become more common.

“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 colistin-resistant bacteria. Until new treatments are available, we must use the knowledge we have to start ‘stemming the tide of AMR’ now – good infection control to prevent the spread of antibiotic resistance combined with only using antibiotics when needed (antimicrobial stewardship).”

 

Prof. Brendan Wren, Professor of Microbial Pathogenesis and Dean of Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, said:

“It is inevitable that there will be colistin-resistant bacteria in Europe. This is yet another example of the step-wise erosion of our arsenal of antibiotics. We have to be prudent with their administration not just to humans, but their indiscriminate use in rearing livestock.”

 

Prof. Christopher Thomas, Professor of Molecular Genetics, University of Birmingham, said:

“Firstly, this illustrates the value of whole genome sequencing (WGS) technology as a tool for monitoring bacterial samples, because it provides a complete catalogue of genetic information which can be checked quickly when a new threat is discovered.

“Second, without further information about this latest story it is difficult to say whether the evidence points at recent spread from China or effectively independent evolution/isolation in Europe. When one looks at the sequence of the mcr-1 gene one finds that many other bacteria carry a similar gene so the gene and its function may be widespread already. I would therefore say that it is quite possible that the use of certain antimicrobials may have selected the emergence of this gene independently in Europe.

“Third, in the case from China the resistance was not linked to lots of other resistance genes but the worry is that it could easily become linked by common genetic processes in bacteria. Therefore it is just a matter of time before worse combinations of resistance genes are likely to appear. Since colistin is one of the last resort antibiotics this is therefore very worrying.”

 

Prof. Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:

“The new data emerging on colistin-resistant bacteria in China and Denmark add to growing concerns about antimicrobial resistance in humans and animals. Colistin is sometimes used as a last-resort antibiotic in vulnerable patients in many European countries including the UK. Resistance to colistin has been known about for some time, but now a new type of resistance has been detected that we were previously unaware of (although it may have existed for years). This new resistance, conferred by a gene called mcr-1, can spread more easily and may have originated in livestock which are much more frequently given colistin than are humans. As with the many previous examples of antimicrobial resistance that are found in both humans and livestock, this situation needs careful monitoring.

“Early detection of new forms of resistance is critical to putting the right policies in place to protect human health. The Danish studies illustrate that new technologies based on the routine sequencing of bacterial genomes can help with this endeavour. We should now be planning to put more effective genomic surveillance in place worldwide so we have a more accurate picture of the extent of the resistance problem.”

 

Prof. Jodi Lindsay, Professor of Microbial Pathogenesis, St George’s, University of London (SGUL, said:

“It is concerning that the new colistin-resistance gene has been found in bacteria in Denmark, and in at least one human.

“We do not know how widespread it might be in Europe at present, but this new study suggests it is present but at very low levels. Now we need to focus on how quickly and how far it will spread. This will be dependent on how much colistin we use, and in human medicine this is currently not very much. But the more we have to use it to treat infections because all other antibiotics have failed, the more resistance we will likely see. A further concern is that the colistin resistance gene is carried on a plasmid, a mobile piece of DNA that transfers between bacteria, and this plasmid has the potential to carry other resistance genes. That means use of other antibiotics that are used much more often could also encourage the selection and spread of colistin resistance.  We need to think very carefully about how we use our current antibiotics and restrict their use wherever we can.”

 

All our previous output on this subject can be seen here

 

Declared 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.

Prof. Brendan Wren: No conflicts of interest to declare

Prof. Chris Thomas: I can declare that I work on resistance plasmids and therefore have an interest in people thinking that studies on plasmids are important.  I also work on antibiotic biosynthesis and production of new antibiotics which might be needed if current antibiotics fail. I am also Treasurer of the Microbiology Society.

Prof. Mark Woolhouse: No conflicts of interest to declare

Prof. Jodi Lindsay: has acted as a consultant to Pfizer on staphylococcal vaccines.

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