Antibiotics for veterinary use: exposure of animals difficult to assess for 2014; levels of resistance that continue to fall
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News of 06/11/2015
To mark European Antibiotic Awareness Day, ANSES today hosted a half-day event to discuss antimicrobial resistance and its impact on human and animal health. On this occasion, the Agency is publishing the results of a national campaign to monitor sales of veterinary medicinal products containing antibiotic agents carried out by the French Agency for Veterinary Medicinal Products (ANMV). There are two main points to be noted: first, the sales figures for 2014 reflect an increase in tonnages which seems to have been caused by distributors or practitioners ordering advanced stocks, in anticipation of the implementation of the new provisions of the French Act on the Future of Agriculture, Food and Forestry, which ends the system of discounts and rebates. It is therefore not possible to use the results for 2014 to assess the actual use of these drugs and consequently the real exposure of animals to antibiotics. On the other hand, more specifically, regarding critical antibiotics, the 2014 results show a decline in exposure to 3rd and 4th generation cephalosporins and to fluoroquinolones by 12.0% and 3.5% respectively, compared to 2013. These decreases represent considerable progress, as these classes of antibiotics are considered particularly important in human medicine. These encouraging results are confirmed by the report of RESAPATH (French surveillance network for antimicrobial resistance in pathogenic bacteria of animal origin), which is coordinated by the ANSES Lyon and Ploufragan laboratories. Resistance to antibiotics, particularly to critical antibiotics, thus continues to decrease overall, although efforts must continue in some production sectors.
Antimicrobial resistance is a major public health concern, in both human and veterinary medicine. In France, many initiatives to promote the rational use of antibiotics have been implemented (national EcoAntibio Plan 2017, awareness-raising in many sectors about good practice and the rational use of antibiotics, an Act for the Future of Agriculture, Food and Forestry, etc.).
The French Agency for Veterinary Medicinal Products (ANSES-ANMV) established national monitoring of sales of veterinary antimicrobials in 1999 in collaboration with the French Union for the Veterinary Medicinal Product and Reagent Industry (SIMV). The information gathered through this national monitoring scheme is one of the indispensable elements, together with the monitoring of bacterial resistance carried out by RESAPATH, for assessing the risks associated with antimicrobial resistance.
Tracking of sales of antibiotics in 2014: an atypical year
The year 2013 saw the lowest tonnage of antibiotics sold since 1999, all animal species combined. A total of 699 tonnes of antimicrobials were sold. In 2014, this total increased by 11.8% (to 781.5 tonnes). This can be explained by the fact that distributors and veterinarians stocked up on drugs containing antibiotics ahead of the end of reductions, discounts and rebates that came into force on 1 January 2015 under the Act on the Future of Agriculture, Food and Forestry. It has been estimated that approximately 3 to 4 months supply was bought up.
Each year, the Animal Level of Exposure to Antimicrobials indicator (ALEA) is calculated on the assumption that all antibiotics sold in the year have been administered to animals reared in France. If the animals' exposure to antibiotics were calculated on the basis of this assumption for 2014, exposure would be overstated. It is therefore inappropriate to make a thorough study of the ALEA by animal species and class of antibiotics for 2014.
For this reason, the ANMV will take account of the combined sales for both 2014 and 2015 in the report it will publish in 2016, in order to smooth over a possible "stocking up" effect.
However, it should be noted that the results for 2014 show a decline in exposure to 3rd and 4th generation cephalosporins and to fluoroquinolones (by 12.0% and 3.5% respectively). Between 2013 and 2014, exposure to 3rd and 4th generation cephalosporins decreased by 11.7% in cattle, 36.8% in pigs and 3.2% in domestic carnivores.
Concerning fluoroquinolones, between 2013 and 2014, all animal species combined, exposure declined (by 3.5%). Over the last two years, exposure to fluoroquinolones increased by 21.5% in poultry, but fell by 7.9% in cattle, by 3.0% in pigs and by 1.3% in domestic carnivores.
These decreases represent considerable progress, as these classes of antibiotics are considered particularly important in human medicine, because they are among the only alternatives for the treatment of certain infectious diseases in humans.
Levels of resistance to antibiotics continue to fall
The RESAPATH network collects the data of antimicrobial sensitivity assays (antibiograms) of pathogenic bacteria of animal origin isolated from sick animals. It is thus able to monitor the trends in antimicrobial resistance in bacteria pathogenic to animals, detect the emergence of certain antimicrobial resistance phenomena, and characterise the molecular mechanisms. RESAPATH continued to develop in 2014, with the total number of member laboratories rising from 67 in 2013 to 69 in 2014. In 2014, 36,989 antibiograms were collected (compared with 33,428 in 2013).
Declining trends in resistance have been observed since 2006 for most antibiotics and in all sectors. This continued to be the case in 2014.
On resistance to critical antibiotics:
For the 3rd and 4th generation cephalosporins, a sharp decline has been observed in recent years among hens and chickens (22.5% in 2010, 5.1% in 2014), pigs and turkeys. Resistance is declining in domestic carnivores, and stable in Equidae. In contrast, increased resistance, which should be closely monitored, has been observed in calves.
For fluoroquinolones, a general downward trend is observed. Resistance is declining in cattle and dogs, and is stable in other species. The rate is low among laying hens and chickens, turkeys and Equidae.
Finally, 2014 shows a downward trend of multi-resistance phenomena (resistance to at least three classes of antibiotics). Levels of multi-resistance nonetheless vary according to the animal species: it is notably higher in cattle, pigs, horses and dogs than in the poultry sectors.
Continuing efforts to achieve our goals
The exposure of animals to critical antibiotics, after a stable period, has declined in recent years. In parallel, levels of resistance to these classes of antimicrobials are also falling. However, the falls observed are greater in some animal sectors where specific measures have been taken. For instance, following action taken by the pig sector to voluntarily limit the use of 3rd and 4th generation cephalosporins, exposure in pigs dropped by 78.2% between 2010 and 2014.
There is therefore every reason to continue these efforts to achieve the objective of reducing the use of cephalosporins and fluoroquinolones by 25% in three years (taking 2013 as the reference year) set by the Act on the Future of Agriculture, Food and Forestry. To achieve this objective will require the continuation of actions already undertaken and the application of new measures, in particular in the sectors that use large quantities of these classes of compounds.
Veterinary pharmacovigilance: continuous monitoring of the risks and benefits of veterinary medicinal products
The French Agency for Veterinary Medicinal Products (ANMV), within ANSES, is the competent authority for risk assessment and management of veterinary medicinal products in France. It is specifically responsible for implementing the veterinary pharmacovigilance system, whose objective is continuous monitoring of the risks and benefits of veterinary medicines after they are placed on the market, to help ensure that they are used safely.
The Agency today released its annual report on veterinary pharmacovigilance. Between 2013 and 2014, the number of declarations increased by 12.6%. In 2014, the ANMV thus recorded in its national database 3593 cases of adverse effects in animals, 44% of which were deemed to be severe adverse effects.
As in previous years, the very great majority of adverse effects reported in 2014 concerned domestic carnivores, with 83.9% of declarations concerning dogs and cats. Declarations concerning cattle accounted for 8.1% of reports. For other species, declarations accounted for less than 3% per species.
Pharmacovigilance also concerns suspicions of lack of efficacy, information on possible risks to the environment, and the validity of withdrawal periods for veterinary medicines. However, cases of adverse effects in animals are still in a significant majority, because they represent 91% of reports. Suspicions of lack of efficacy account for 8% of declarations and other cases less than 1%.
Besides, in 2015 the ANMV was heavily involved in discussions on the revision of EC veterinary pharmaceutical legislation.