Reducing the use of antibiotics in animals leads to a rapid and lasting decrease in bacterial resistance
Antibiotics select for bacteria that carry antibiotic resistance genes. Can reducing the use of these drugs help reduce bacterial resistance? In other words, to what extent is antimicrobial resistance reversible? “The answer to this question isn't as obvious as it may seem”, explains Lucie Collineau, a researcher in the Epidemiology and Surveillance Support unit of ANSES’s Lyon Laboratory. “Bacterial resistance to antibiotics depends on many different factors. For example, there can be cases of multidrug resistance, where the use of one antibiotic co-selects for resistance to another one. There was therefore no certainty that antimicrobial resistance could be reduced, especially since we didn’t know how long it might take”.
Scientists at ANSES carried out two research projects on this topic. One focused on the resistance of Escherichia coli to fluoroquinolones and third- and fourth-generation cephalosporins in calves, dogs and cats, while the other investigated E. coli resistance to colistin in calves and swine. Both studies were funded under the Ecoantibio plan. They showed that the proportion of resistant bacteria decreased very sharply just one to two years after antibiotic use was reduced.
Antimicrobial resistance: a threat to animal and human health
The antibiotics studied were selected because of their importance for both human and animal health. Fluoroquinolones and cephalosporins are considered critically important antibiotics, which means they are used as a last resort to treat serious diseases in humans and animals. Their use in veterinary medicine is therefore strictly regulated. The scientists chose to focus specifically on E. coli bacteria carried by calves, dogs and cats because no previous studies had examined the impact of reducing the use of these antibiotics in these species.
As for colistin, although it is not classified in France as a critically important antibiotic, it is used as a last resort against multidrug-resistant bacteria in human medicine. Following the discovery of bacteria resistant to this antibiotic, recommendations were issued in 2016 to reduce its use in livestock. The study focused on calves and swine, as E. coli resistance is higher in these animals.
Capitalising on the long-term monitoring of trends in antimicrobial resistance
The scientists based their studies on data from Résapath (the French surveillance network for antimicrobial resistance in pathogenic bacteria of animal origin), which has monitored trends in antibiotic resistance in domestic animals in France since 1982.
“We’re fortunate to have data covering such a long period”, explains Claire Chauvin, a scientist in the Epidemiology, Health and Welfare unit of ANSES’s Ploufragan-Plouzané-Niort Laboratory. “The network collects the results of antibiotic resistance tests (antibiograms) performed by veterinary laboratories on bacteria isolated from animals during veterinary consultations. This gives us access each year to thousands of antibiograms and bacterial strains for each animal species. It provides much broader coverage than the mandatory surveillance carried out at European level, which only concerns food-producing animals at the slaughter stage”.
The scientists compared the Résapath data with data on exposure to antibiotics in animals, monitored each year within ANSES by the French Agency for Veterinary Medicinal Products.
Antimicrobial resistance and antibiotic exposure decrease simultaneously
“The curves showing the proportion of resistant bacteria and the level of animal exposure to antibiotics closely overlap, with only a one- to two-year lag depending on the animal species”, note the scientists.
For example, the resistance of E. coli to colistin rose until 2010-2011 and then declined, dropping from 40% resistant bacteria to around 5-10% today, depending on the animal species.
Exposure of animals to third- and fourth-generation cephalosporins and to fluoroquinolones decreased respectively by 94% and 88% between 2011 and 2021. At the same time, the proportion of resistant E. coli decreased from 20% to 7% or even 5%, depending on the animal species and the antibiotic.
Although some substitution of these antibiotics with other classes considered less important for human and animal health was observed, this shift did not lead to any co-selection of resistance to the antibiotics under study.
“Several factors played a role in reducing antibiotic use in animal health. The regulations were one of the driving forces, with quantified targets set for reducing animal exposure to critically important antibiotics and to colistin – targets that were achieved and even exceeded. That being said, farmers and veterinarians had already started reducing antibiotic use before the regulations came into force. Vaccination and improvements in farming practices also helped prevent infections and therefore reduce the need for antibiotics”, affirms Collineau.
The results of both studies show that this collective effort has paid off, leading to a rapid and lasting decrease in resistance to these antibiotics, which has now reached very low levels.