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ECDC/EFSA/EMA Second Joint Report on the Integrated SCIENTIFIC REPORT APPROVED: 28 June 2017 doi: 10.2903/j.efsa.2017.4872 ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report European Centre for Disease Prevention and Control (ECDC), European Food Safety Authority (EFSA) and European Medicines Agency (EMA) Abstract The second ECDC/EFSA/EMA joint report on the integrated analysis of antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in bacteria from humans and food-producing animals addressed data obtained by the Agencies’ EU-wide surveillance networks for 2013–2015. AMC in both sectors, expressed in mg/kg of estimated biomass, were compared at country and European level. Substantial variations between countries were observed in both sectors. Estimated data on AMC for pigs and poultry were used for the first time. Univariate and multivariate analyses were applied to study associations between AMC and AMR. In 2014, the average AMC was higher in animals (152 mg/kg) than in humans (124 mg/kg), but the opposite applied to the median AMC (67 and 118 mg/kg, respectively). In 18 of 28 countries, AMC was lower in animals than in humans. Univariate analysis showed statistically-significant (p < 0.05) associations between AMC and AMR for fluoroquinolones and Escherichia coli in both sectors, for 3rd- and 4th-generation cephalosporins and E. coli in humans, and tetracyclines and polymyxins and E. coli in animals. In humans, there was a statistically-significant association between AMC and AMR for carbapenems and polymyxins in Klebsiella pneumoniae. Consumption of macrolides in animals was significantly associated with macrolide resistance in Campylobacter coli in animals and humans. Multivariate analyses provided a unique approach to assess the contributions of AMC in humans and animals and AMR in bacteria from animals to AMR in bacteria from humans. Multivariate analyses demonstrated that 3rd- and 4th-generation cephalosporin and fluoroquinolone resistance in E. coli from humans was associated with corresponding AMC in humans, whereas resistance to fluoroquinolones in Salmonella spp. and Campylobacter spp. from humans was related to consumption of fluoroquinolones in animals. These results suggest that from a ‘One-health’ perspective, there is potential in both sectors to further develop prudent use of antimicrobials and thereby reduce AMR. © 2017 European Centre for Disease Prevention and Control, © European Food Safety Authority and © European Medicines Agency. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. Keywords: antimicrobial consumption, antimicrobial resistance, public health, food-producing animals, ecological analysis, logistic regression, partial least square path modeling Requestor: European Commission Question number: EFSA-Q-2016-00029 www.efsa.europa.eu/efsajournal EFSA Journal 2017;15(7):4872 ECDC, EFSA and EMA second joint report, JIACRA Acknowledgements: The representatives of the MSs and other members of the different networks are thanked for providing data for the surveillance networks: at ECDC: EARS-Net, ESAC-Net and FWD-Net, at EFSA: Scientific Network for Zoonosis Monitoring Data and at EMA: ESVAC Network Sales. This joint report is based on data provided by the above-mentioned networks and on the major contributions of the following experts: at ECDC: Ole Heuer, Elias Iosifidis, Chantal Quinten, Klaus Weist, Therese Westrell and Dominique Monnet, at EFSA: Pierre-Alexandre Belœil, Ernesto Liebana, John Threlfall and Christopher Teale (Chair) and at EMA: Claire Chauvin, Kari Grave, Christina Greko, Gerard Moulin, Stephanie Bougeard, Jana Dall’aglio, Joana Fonseca, Kristine Ignate, Zoltan Kunsagi and Jordi Torren-Edo. Correspondence: • ECDC: [email protected] • EFSA: [email protected] • EMA: [email protected] Procedures for adoption of the report: Representatives of the different surveillance/monitoring networks of the MSs in charge of providing the data and the European Union Reference Laboratory for Antimicrobial Resistance (EURL-AR) have been consulted at the finalisation of the preparation of the joint report. ECDC, EFSA and EMA have each established their own procedure for endorsement or adoption of the joint report according to their internal rules. ECDC adopted the report on 28 June 2017, after consultation with the European Antimicrobial Resistance Surveillance Network (EARS-Net), the European Surveillance Antimicrobial Consumption Network (ESAC-Net), the Food- and Waterborne Diseases and Zoonoses Network (FWD-Net), and the ECDC Advisory Forum. EFSA approved the report on 28 June 2017, after consultation of its Scientific Network for Zoonosis Monitoring Data. EMA adopted the report on 28 June 2017. Before endorsement the report was circulated for consultation to the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) network. The report was circulated on 4 July 2017 to the CVMP plenary meeting for information. Suggested citation: ECDC (European Centre for Disease Prevention and Control), EFSA (European Food Safety Authority), and EMA (European Medicines Agency), 2017. ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals – Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report. EFSA Journal 2017;15(7):4872, 135 pp. doi:10.2903/j.efsa.2017.4872 ISSN: 1831-4732 © 2017 European Centre for Disease Prevention and Control, © European Food Safety Authority and © European Medicines Agency. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. www.efsa.europa.eu/efsajournal 2 EFSA Journal 2017;15(7):4872 ECDC, EFSA and EMA second joint report, JIACRA Summary This report on integrated analyses of potential relationships between the consumption of antimicrobial agents (AMC) and the occurrence bacterial of antimicrobial resistance (AMR) in humans and in food-producing animals was produced by the European Centre for Disease Prevention and Control (ECDC), the European Food Safety Authority (EFSA) and the European Medicines Agency (EMA). This is the second report of its kind prepared by the three agencies following a request from the European Commission (EC). The data included in the analyses and the results presented in the report pertain to 2013, 2014 and 2015 and were obtained through five different surveillance/monitoring networks managed by the agencies to collect annual data on AMC and AMR in humans and in food-producing animals in the EU/EEA Member States (MSs) and in Switzerland. The data used in the analyses were collected as part of clinical and epidemiological surveillance/monitoring in both humans and food- producing animals, and were not collected specifically for the purpose of this report. The integrated analyses of data from humans and animals presented here were based on the ‘One-Health’ approach and focused on particular combinations of antimicrobials and bacterial species considered of importance for public health. Compared to the first JIACRA report, the number of countries reporting AMC data increased in both humans (30, previously 28) and food-producing animals (29, previously 26). AMC data from humans are commonly reported as defined daily doses (DDD) per 1,000 inhabitants and per day, whereas the corresponding data in food-producing animals are typically expressed in milligrams of active substance per kilogram of estimated biomass and per year. As a fully comparable measurement unit is not available, AMC data in humans were converted into mass of active substance per kilogram of estimated biomass to make the comparison as consistent as possible. To facilitate the comparison of AMC and AMR and for the sake of consistency with the first JIACRA report, a summary indicator of microbiological resistance (SIMR) was calculated for food-producing animals on the basis of the weighted mean by estimated biomass of the proportions of drug-resistant bacteria in each animal species included in the indicator. For data referring to 2013, the SIMR in bacteria from food-producing animals addressed AMR data covering cattle, pigs and broilers, whereas, for data referring to 2014–2015, AMR data on broilers, fattening turkeys, fattening pigs and cattle under 1 year of age were included. An additional SIMR in bacteria from poultry was also constructed based on AMR data on broilers and turkeys for 2014–2015. These differences reflect changes in the EU legislation on AMR monitoring in food-producing animals implemented in 2014. SIMR were compared to corresponding AMC in food-producing animals. To date, AMC data in food-producing animals are not available by species in the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) reports, whereas, in this report, an attempt to infer AMC at the animal species level was made. Technically derived estimates of sales of antimicrobials in pigs and poultry were used
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