Not just for animals: bacterial resistance to the antibiotic colistin is also significant for humans

Colistin is a polypeptide antibiotic from the polymyxin group. The antibiotic is used primarily in veterinary medicine, with a vast range of applications for the treatment of bacterial intestinal diseases alongside other infections. 

If an antibiotic is no longer effective against certain bacteria, these bacteria have developed resistance to the substance. Colistin resistance is present when the minimum concentration of the substance colistin required to inhibit bacterial growth exceeds a specified limit value. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST), Escherichia (E.) coli and Salmonella are considered colistin-resistant if they continue to grow at concentrations of over 2 mgshort formilligram colistin per liter (mgshort formilligram/l) of culture medium.

In veterinary medicine, colistin has long been of considerable importance, particularly for the treatment of gastrointestinal tract infections in livestock. The amounts of colistin used have decreased significantly in recent years, following the discovery of a transmissible resistance gene against colistin in intestinal bacteria and a corresponding recommendation from the European Medicines Agency (EMA). In Germany, 127.4 tonnes of polypeptide antibiotics were dispensed to vets and veterinary dispensaries in 2011, and 31.0 tonnes in 2024. The vast majority of these were colistin. Compared with 2011, the first year such data was recorded, this represents a decrease of 75.7 per cent.

Compared to other antibiotics, colistin is rarely used in human medicine because it is not well tolerated by humans. Possible adverse effects include, for example, damage to the kidneys or the nervous system. The significance of colistin in human medicine lies in the treatment of severe infections caused by certain species of germs, known as Gram-negative germs, which are resistant to most commonly used antibiotics – including carbapenems, which are used to treat severe infections. These treatments are rarely required, as the number of infections caused by such germs in Germany has so far been low. Furthermore, there are other, better-tolerated alternatives available. 

The occurrence of colistin resistance in intestinal bacteria such as Escherichia coli and Salmonella enterica has been observed in animals for several years now. In most cases, colistin resistance is transmitted between bacteria via genes on a mobile genetic element (plasmid). A plasmid is a ring-shaped DNA molecule that can carry genes for various properties and can be transferred between different bacteria. The gene for transmissible colistin resistance, discovered in 2015, is called mcr-1. It was first described in China and has since been detected in bacteria from livestock around the world. The gene was also identified during retrospective analysis of bacteria from older samples, meaning its prevalenceClose dialogprevalencePrevalenceTo glossary in Germany has been documented since at least 2008.

Consequently, research, including studies involving the BfRshort forGerman Federal Institute for Risk Assessment, has led to investigations into further transmissible genes for colistin resistance and their variants in livestock (mcr-2 to mcr-10). The discovery of further genes of this type is still to be expected. It has now also been shown that a variant of the gene can be transmitted between bacteria from animals and humans (External Link:Microbiology Spectrum 2023).

As part of zoonosis monitoring, the federal institutions and German federal states ("Laender") have been systematically investigating colistin resistance in zoonotic pathogens and natural inhabitants of the intestine (commensal germs) since 2010. Between 2010 and 2015, the highest proportions of colistin-resistant germs were detected in E. colishort forEscherichia coli from the turkey meat (11.7%) and chicken meat (6.0%) food chains. In 2024, 5.2% of isolates from turkey and 1.6% of Escherichia coli isolates from chicken meat exhibited colistin resistance. In isolates from pork and beef, no colistin resistance was observed since 2021. These resistance genes have not yet been detected in Germany in breeding poultry or in dairy products. Of the E. coli isolates that tested as colistin-resistant, the majority of those examined by the BfRshort forGerman Federal Institute for Risk Assessment carried the transmissible mcr-1 gene. Since 2014, the prevalence of E. colishort forEscherichia coli resistance to colistin in broiler turkeys and chickens raised for meat production at the time of slaughter has declined significantly. In calves raised for meat production and pigs raised for meat production, its occurrence was sporadic at the time of slaughter as early as 2014.

Current data on the resistance of microorganisms in slaughter animals and in food are available at: External Link:https://zoonotify.bfr.berlin/.

Colistin resistance is also observed in other intestinal bacteria. In the case of Salmonella, it is of immediate significance to humans due to the pathogenic properties of these bacteria. Here too, data on the prevalence of this resistance are available on the ZooNotify website, although the number of isolates examined is low for most sample materials.

Resistance genes of this type have also been sporadically detected in other bacteria (e.g. Citrobacter spp., Klebsiella spp., Acinetobacter spp.), which highlights their transmissibility between bacteria of different genera. However, these bacteria are not tested for resistance in routine checks on healthy animals and food.

Hygiene measures during the transport, storage and preparation of food offer protection against germs that are resistant to antibiotics. For example, raw meat should be heated to 70 degrees Celsius for at least two minutes, right through to the centre, before consumption. When handling raw meat, care should be taken to ensure that germs are not transferred to other foods via the hands or articles (e.g. knives, chopping boards).

The BfRshort forGerman Federal Institute for Risk Assessment has published the leaflet “External Link:Consumer advice: Protection against foodborne infections in private households”, which summarises the most important hygiene rules for handling food. The tips in the leaflet apply equally to resistant and sensitive germs. 

Antibiotics should only be used preventively in individual animals in exceptional cases. In its External Link:guidelines on the prudent use of antimicrobials in veterinary medicine, the German Veterinary Association recommends replacing routine prophylaxis. Similar guidelines have also been issued by the External Link:European Commission.

In the context of group and herd treatments, animals that have not yet fallen ill are often treated as well. In such cases, the veterinarians responsible assume that these animals have already been exposed to the pathogens. The use of antibiotics is intended to prevent the spread of the disease and avoid more complex treatment of animals that are already ill. Colistin is used in the same way as all other substances in this context. 

Since 2017, colistin has been classified by the World Health Organisation (WHO) as one of the “highest priority critically important antimicrobials”. These are substances with the highest priority within the group of particularly important antibiotics. The WHO provides a rationale on the one hand by citing the increasing frequency of colistin use for the treatment of serious human infections, particularly with Enterobacterales and Pseudomonas aeruginosa, in various parts of the world. Furthermore, the WHO refers to the discovery of transmissible resistance to colistin and the spread of this resistance through the food chain. The “Antimicrobial Advice ad hoc Expert Group” (AMEG), based at the European Medicines Agency (EMA), has made the classification for polymyxins, including colistin, as Category B (“Restrict”). These antibiotics should only be used to treat clinical conditions if there are no other antibiotics of effective efficacyClose dialogefficacyPositive Predictive ValueTo glossary available from categories C (“Caution”) and D (“Prudence”). Substances in categories C and D are of lesser importance for human treatment, partly because there are still many alternatives to them for treating certain infections. In Germany, the use of colistin and other Category B substances in food-producing animals is subject to an obligatory antibiotic susceptibility testing requirement. This means that, prior to use, the sensitivity of a bacterium to various antibiotics must be tested (Section 13 of the External Link:Veterinary Dispensary Ordinance). 

When conducting an assessment of the frequency of treatment in farms subject to the antibiotic minimisation scheme, treatments with substances in Category B are counted three times in the benchmarking system. Both regulations aim to reduce the use of substances in this category as much as possible.