Context: In the early 2000s, the resistance to critically important antimicrobials (CIAs) for some human diseases emerged in bacteria isolated from food-producing animals, including cattle. Calves, which are particularly susceptible to digestive diseases, are considered as a reservoir of Enterobacteriacae carrying antimicrobial resistance (AMR) determinants. In March 2016, the French animal health authorities have enacted a decree restraining the prescription of CIAs in veterinary medicine. The aim of the study was to describe the temporal evolution of AMR of E. coli isolated from calves with digestive disorders in France to two CIAs in order to assess the likely impact of the French regulations.
Materiel and method: Data collected between 2006 and 2016 by the French surveillance network for AMR in diseased animals referred to as RESAPATH were analysed. We investigated the trend in resistance of E.coli isolated from calves to CIAs, namely fluoroquinolones and third generation cephalosporins, represented by enrofloxacin and ceftiofur. Resistance trends were explored using generalized additive models (GAM) applied to time-series by antibiotic and periods of statistically significant change in these trends were identified using the first derivatives.
Results: The resistance levels to ceftiofur stayed below 10 % over the period, but the resistance levels to enrofloxacin fluctuated between 17 and 32 %. The resistance trend to ceftiofur significantly increased from 4.3% [3.1; 5.5] in January 2006 to 7.9% [7.1; 8.6] in November 2011, then stabilized around 8 % and decreased from 7.6% [7.0; 8.3] in January 2015 to 6.1% [5.1; 7.0] in December 2016. The resistance trend to enrofloxacin was stationary around 32 % from January 2006 to November 2010 and then decreased from 31.0% [29.4; 32.7] to 17.3% [15.6; 18.9] in December 2016.
Discussion: Even if the levels of the E. coli resistance to CIAs were low, they are concerning because these antibiotics are of highest priority for human medicine. The decline of resistance to enrofloxacin predated the publication of the decree on CIAs and even appeared before the publication of the EcoAntibio plan (November 2011), the first French action plan in Animal Health promoting the responsible use of antimicrobials. Thus the variations of resistance to enrofloxacin did not directly result from control measures. In addition, they did not follow the decrease of antibiotic consumption after 2011. Contrariwise, the resistance trend to ceftiofur stabilized and decreased after the publication of the EcoAntibio plan, in parallel with the decline in ceftiofur consumption since 2012. The decline in resistance started before the implementation of the decree; nevertheless the perspective of the regulation might have supported the drop.
Conclusion: This study was the first to describe the evolution of resistance to CIAs of E.coli isolated from calves with digestive disorders in France. While control measures and reduction of consumption seem to have reversed the trend of resistance to ceftiofur, they cannot sufficiently explain trend variations of resistance to enrofloxacin. The differences between the two antimicrobial might partly be explained by the different resistance mechanisms involved. These results highlight the need for a comprehensive approach to the fight against AMR and the importance of awareness of all stakeholders involved.