When conventional treatment options have been exhausted, doctors turn to less safe “last-resort” drugs. Colistin is such a last-resort antibiotic. Long used in veterinary medicine, colistin is also essential in treating severe bacterial infections in human cases where other antibiotics have lost their efficacy due to resistant strains of bacteria.
Efficacy of colistin under threat
In November 2015, a Chinese research group captured the image of MCR-1, a gene capable of rendering bacteria resistant to colistin. The gene can spread from one bacterium to the next through plasmids. The results indicate that the gene may have developed and evolved in production animals with the increased use of colistin, and has since transferred to human pathogens. The first observations of transferrable colistin resistance were made in southern China, where colistin is very commonly used in production animals.
The European Medicines Agency collected a multidisciplinary group of top experts to evaluate the risk of widening colistin resistance due to the use of the antibiotic in production animals. One of the members was DVetMed Merja Rantala, who has served as a member of the European Medicines Agency’s Antimicrobial Working Party (AWP) since 2011. The recommendation was released in July 2016.
Use of colistin in animals to be cut by 65%
Colistin is the fifth most popular antibiotic used on production animals in Europe. Small amounts of the gene which can confer resistance have been found in animal bacteria or animal-derived foodstuffs in several European countries. With continued use of colistin, the resistance conferred by the gene could spread rapidly. Colistin resistance may transfer to human pathogens via bacteria from production animals, or foods that contain such bacteria. To safeguard the efficacy of colistin, the expert group recommends that its use in production animals in the EU be cut dramatically. “The EU has set a strict goal to reduce the use of colistin in production animals by 65% during the next three to four years without increasing the use of other antibiotics. This is a good, concrete goal,” states Rantala.
“For each country, the use of colistin should not exceed 5mb per PCU (population correction unit). This goal forces member states with widespread use of colistin to act. The biggest users of colistin are Italy, Spain, Portugal and Germany. Finland does not use colistin in production animals at all – thanks to the excellent Finnish health care system, production hygiene and sensible policies regarding antibiotics,” explains Rantala.
Discovered in the 1950s
Colistin has been used on humans since the 1960s, but its use decreased rapidly once new, safer options became available. Now that more drug-resistant strains of bacteria are appearing, medical professionals have had to bring colistin back from “retirement”. It is currently used to treat general infections caused by Gram-negative bacteria such as E. coli in hospital patients, if safer antibiotics have proven ineffective. Colistin is most commonly used on humans in countries which have the most severe problems with antibiotic resistance.
In veterinary medicine, colistin has been used since the 1950s. Its most common application is for the treatment of E. coli infections in the digestive tracts of pigs and fowl. For practical reasons, drugs are typically administered to productions animals in large groups, which means that the amounts are large. Most of the world’s colistin is used in veterinary medicine.
“Colistin has been in veterinary use in Europe for decades without significant problems with resistance,” explains Rantala. It took a long time to discover this transferring resistance mechanism, even though resistance researchers are not surprised by the new discovery. The MCR-1 gene has been retroactively identified in bacterial strains which were isolated in the 1980s. Researchers around the world are now going through their freezers and screening bacteria for colistin resistance.”
The recommendation poses a significant challenge to countries which are currently using colistin heavily. On the other hand, countries which use little or no colistin are proof that it is possible to raise production animals without the antibiotic. The recommendations emphasise that the overall use of antibiotics should not increase. This means that any measures seeking to reduce antibiotic use must focus on improving animal health care and the production conditions, which Rantala believes is a very positive side-effect.
Antibiotics only when necessary
“Even though colistin is not used on animals in Finland, and we have not discovered any colistin resistance, we must still pay attention to the use of antibiotics. Antibiotic resistance in pets in particular is increasing in Finland at such a pace that it is endangering the treatment of severe infections. The discovery of the new resistance mechanism again highlights the importance of constant resistance monitoring and of research in this area,” Rantala muses.
- DVetMed Merja Rantala, tel. +358 2941 57415
- European Medicines Agency press release on colistin: Countries should reduce use of colistin in animals to decrease the risk of antimicrobial resistance
- European Medicines Agency advice on colistin: Updated advice on the use of colistin products in animals within the European Union: development of resistance and possible impact on human and animal health
- Liu et al.: Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis.
- ;16(2):161-8. Epub 2015 Nov 19.
* The population correction unit, or PCU, is a relative unit used to calculate a country’s antibiotic consumption relative to its number of production animals. The application of this unit enables the collection of comparable consumption data on antibiotics from EU member states. More information on the PCU: European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption, 2015. Sales of veterinary antimicrobial agents in 26 EU/EEA countries in 2013 (EMA/387934/2015).