Colistin is an antibiotic used in veterinary medicine, in particular for the treatment of colibacillary infections in animal production sectors.
In human medicine, colistin has long been excluded from treatment protocols because of its toxicity, particularly renal. Since the global dissemination of resistance to the latest generation cephalosporins and carbapenems, colistin has once once more become an antibiotic prescribed for the treatment of severe human infections linked to bacteria resistant to all other therapeutic options.
Given the use of colistin in human medicine, the scientific and medical community has questioned the risk of selection of resistance to colistin in humans following its use in animals. Recent opinions have been formulated, in particular by the European Medicines Agency (EMA) and by ANSES, not recommending, at this stage of knowledge, to include colistin in the list of critical antibiotics used in veterinary medicine, and whose use must be supervised. In particular, the absence of resistance mechanism to colistin transferable between bacteria constituted a strong scientific argument.
November 2015: description of the first resistance mechanism to transferable colistin
On November 18, 2015, the first transferable colistin resistance mechanism (the gene mcr-1) has been described in China in pigs and chickens, from retail meat, as well as in bacterial strains isolated from humans1. The prevalence of this plasmid gene has been estimated at around 20% in animals and around 1% in humans.
The publication of the genetic sequence of the gene mcr-1 led several institutes to search for its presence in other bacterial collections worldwide. To date, in Europe, the gene mcr-1 has been detected in bacterial strains ofEscherichia coli and/or of Salmonella entericaby the European Reference Laboratory for Animal Antimicrobial Resistance (DTU, Denmark)2by the Public Health Reference Laboratory in England3 and by the four ANSES laboratories involved in monitoring animal antimicrobial resistance4. In all these collections, the prevalence of the gene mcr-1 is particularly low.
In addition, no alarming increase in resistance to colistin in bacteria isolated from the poultry and pig sectors has been recorded by ANSES’s various monitoring networks in recent years.
On December 17, 2015, additional data on the distribution of the gene mcr-1 in other world collections have been published4, 5, 6, 7, 8. They confirm a low prevalence of this gene in humans and provide additional molecular elements.
Many works are in progress on this subject, and several questions persist to this day. They relate in particular to:
- gene prevalence mcr-1 in the different sectors, animals and humans, in France, in Europe and in the world. The various samplings of the bacterial collections studied make it possible to conclude that this gene has been detected, and not yet at prevalence levels validated on an epidemiological level;
- the age of the dissemination of the gene mcr-1 in animal and human bacterial flora. Most of the published data relate to rather recent strains (> 2010). Its greater or lesser seniority in the animal sectors is an important element of assessment in the risk analysis;
- the levels of colistin resistance (low or high) of bacteria possessing the gene mcr-1, whose therapeutic impact is directly dependent. Also, the gene mcr-1 is not present in all bacteria resistant to colistin, which raises the question of the part of this mechanism in the broader explanation of this resistance;
- the possibilities (or not) of co-selection of the gene mcr-1 by the use of antibiotics other than colistin, such as those widely used in veterinary medicine (tetracyclines, sulfonamides) or those of critical importance for humans and with plasmid dissemination (latest generation cephalosporins);
- the diversity of the molecular characteristics of the genetic carriers (types of plasmids) and of the bacterial clones carrying the gene mcr-1on which depend the more or less strong diffusion capacities between bacterial species, between animal species and from animals to humans.
A new analysis of the risks linked to the use of colistin is necessary
The scientific elements recently identified on bacterial resistance to colistin should be taken into account in a new analysis of the risks associated with the use of colistin, particularly in veterinary medicine.
In this context, the EMA wishes to bring together once more the group of experts to this on antimicrobial resistance (AMEG) in order to revise the opinion published in 2013 on the use of colistin in veterinary medicine. Experts from ANSES are part of this group to this.
For many years, ANSES has played a key role in monitoring and alerting on antibiotic resistance phenomena in the animal world, and in connection with the possible consequences for public health. This work is carried out thanks to the responsiveness of all the systems it manages, regulatory monitoring at the slaughterhouse and in food, and within the framework of the activity of the Salmonella and Résapath networks set up several decades ago. years in France. At the same time, ANSES-ANMV, through its involvement with the EMA and its annual monitoring of veterinary antibiotic consumption, provides essential information on the exposure of animals to antibiotics, which is usefully compared with the levels of resistance observed.
ANSES will therefore revise the risk assessment carried out in its scientific opinion (opinion no. 2015-SA-0118) (PDF) on the classification of colistin as a critically important veterinary antibiotic.
