Where does antimicrobial resistance come from?
Antibiotics are substances that fight infection-causing bacteria. They began to be used on a large scale after World War II. They led to major medical breakthroughs, capable of treating previously incurable diseases and increasing human life expectancy by more than 10 years. However, their frequent and sometimes unjustified (treatment periods that are too short or too long, unsuitable doses) use, in both human and veterinary medicine, has contributed to the emergence of bacteria that are resistant to these treatments, via the selection of strains capable of surviving antibiotics.
Today, numerous bacteria are resistant to several different antibiotics (multidrug resistance). This phenomenon compromises the efficacy of the available treatments and threatens human and animal health. There are some situations that result in therapeutic dead-ends, when there are no longer any antibiotics effective against a bacterium.
A general problem
Some resistant bacteria can be transmitted from animals to humans, and vice versa. Bacteria carrying antimicrobial resistance genes are also found in the environment. Combating antimicrobial resistance therefore requires an overall approach, including humans, animals and the environment. Preserving the efficacy of antibiotics requires rational use, along with careful monitoring of their use and of the emergence and spread of resistance to these substances, for both humans and animals.
What is ANSES's role in combating antimicrobial resistance?
ANSES is responsible for monitoring antimicrobial resistance in veterinary medicine, whether related to livestock farming, food or the environment.
Monitoring and studying bacterial resistance in animals
The National Reference Laboratory for antimicrobial resistance
ANSES is the National Reference Laboratory (NRL) for antimicrobial resistance. As such, it monitors the resistance of bacteria that can contaminate humans via food of animal origin, as part of surveillance plans that have been harmonised at European level.
In particular, the Agency carries out annual surveillance plans, overseen by the Ministry of Agriculture and Food, which monitor developments at national and European level. The NRL also validates authorised methods for testing the resistance of bacteria of animal origin to antibiotics of critical importance to humans.
How does the surveillance plan implemented by the NRL work?
Surveillance focuses on “sentinel” bacteria, such as Escherichia coli, as well as bacteria such as Salmonella and Campylobacter that cause human infections. Samples are collected from healthy food-producing animals.
Depending on the bacterium and farming sector, samples are collected on the farm (surface sampling), at the slaughterhouse (in intestinal contents) or at distribution (in meat). Sampling is random and takes place throughout the year and across the country. Every year, the results are published in France by the Directorate General for Food (DGAL) and at European level by the European Food Safety Authority (EFSA).
Since the start of the monitoring programmes, more and more Escherichia coli strains have been susceptible to all tested antibiotics, regardless of the animal species of origin. The situation varies more greatly for Salmonella and Campylobacter, depending on the sampling conditions, animal species and tested antibiotic.
Since 1982, the French surveillance network for antimicrobial resistance in pathogenic bacteria of animal origin (RESAPATH) has been monitoring changes in resistance to antibiotics for all animal species in France.
The objectives of the RESAPATH network are to monitor trends in antimicrobial resistance in bacteria of importance for animal health (including Escherichia coli), detect the emergence of resistance to antibiotics, and characterise the molecular mechanisms involved. It also provides all of its stakeholders with methodological and scientific support.
Since the start of the monitoring programme, the rate of antimicrobial resistance has decreased to varying degrees depending on the animal sector and antibiotic. In addition, Escherichia coli strains have become less and less multidrug resistant (i.e. resistant to at least three antibiotics). However, there is no room for complacency, since there has been a trend reversal for certain species since 2018: the rate of antimicrobial resistance has increased slightly in cats, dogs and horses and for this last species, there has been an increase in multidrug-resistant E. coli.
Monitoring animal exposure to antibiotics
Monitoring sales of veterinary antibiotics enables the authorities to assess animal exposure to antibiotics and monitor changes in practices for different animal species. The information collected is essential for the assessment of risks associated with antimicrobial resistance in addition to the monitoring of bacterial resistance.
How does the sales survey of veterinary medicinal products work?
ANSES set up this monitoring programme in 1999, in partnership with the French Union for the Veterinary Medicinal Product and Reagent Industry (SIMV). It is based on the annual reporting of sales of antibiotics by the pharmaceutical companies marketing them. These reports cover all authorised veterinary medicinal products and include a breakdown of sales by species. These data can be combined with other sources of information such as reported turnover, prescription surveys, etc.
The data on antibiotic sales volumes do not accurately reflect their use. Recent antibiotics are more potent and require smaller doses of product. In addition, animal populations can fluctuate over time. To assess animal exposure to antibiotics, it is necessary to consider the dosage and duration of administration of the medicinal products and also changes in the population of the species in question. These parameters are taken into account to calculate the Animal Level of Exposure to Antimicrobials (ALEA).
Between 2011 and 2020, overall animal exposure to antibiotics decreased by 45.4%. The objectives of the EcoAntibio plan (2012-2016), which aimed to reduce antibiotic use by 25% within five years, and then of the EcoAntibio 2 plan (2017-2021), whose goal was to ensure that this decline was sustained, were achieved. The EcoAntibio 2 plan also aimed for a 50% reduction in the use of colistin, an antibiotic that is commonly used in veterinary medicine and is reserved for severe cases in human medicine. This objective was also achieved, since this decrease was 66% in 2020, compared to the reference level from 2014-2015
Critically important antibiotics
Certain antibiotics are considered critically important to human health, because they are the only ones or are among the few that can treat serious diseases in humans. Their use is therefore regulated in veterinary medicine and should only be considered as a last resort. After a sharp decrease observed between 2013 and 2016, exposure to fluoroquinolones and third- and fourth-generation cephalosporins seems to have stabilised.
Assessing the risks associated with antimicrobial resistance as part of the marketing of veterinary antibiotics
The French Agency for Veterinary Medicinal Products (ANMV) grants marketing authorisations (MAs) in France for veterinary antibiotics. In this context, it assesses their quality, efficacy and safety for the animal, the user (safety during administration), the consumer of foods of animal origin and the environment, taking into account the risk of development of resistance. It also monitors these medicinal products after they have been placed on the market.
Studying antibiotics and resistant bacteria in the environment
In November 2020, ANSES issued an expert appraisal report on antibiotics and resistant bacteria in the environment. Unlike for animals and humans, the role of the environment in the emergence and spread of antimicrobial resistance has not been widely studied. This was an initial review of contamination of aquatic and terrestrial environments in France by antibiotics, resistant bacteria that are pathogenic for humans, and antimicrobial resistance genes. It also examined the mechanisms that promote the emergence and persistence of antimicrobial resistance in the environment.
Conducting research to better monitor and understand antimicrobial resistance
ANSES's laboratories also carry out multiple research projects to improve knowledge on antimicrobial resistance. These projects may aim to improve the monitoring of antimicrobial resistance, for example by enhancing the methods used to detect resistant bacteria and also by improving the functioning of the monitoring systems.
Other projects aim to better understand how antibiotic-resistant bacteria are selected and spread. To do so, they use an overall approach, taking into account humans, animals and the environment.
International reference activities
ANSES is a Collaborating Centre of the World Organisation for Animal Health (WOAH) for veterinary medicinal products and a Reference Centre for antimicrobial resistance for the Food and Agriculture Organization of the United Nations (FAO). As part of these mandates, the Agency provides advice to these institutions and support to Member States to guarantee the rational use of antibiotics in veterinary medicine and reduce antimicrobial resistance.