Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011 Third ESVAC report An agency of the European Union The mission of the European Medicines Agency is to foster scientific excellence in the evaluation and supervision of medicines, for the benefit of public and animal health. Legal role Guiding principles The European Medicines Agency is the European Union • We are strongly committed to public and animal (EU) body responsible for coordinating the existing health. scientific resources put at its disposal by Member States • We make independent recommendations based on for the evaluation, supervision and pharmacovigilance scientific evidence, using state-of-the-art knowledge of medicinal products. and expertise in our field. • We support research and innovation to stimulate the The Agency provides the Member States and the development of better medicines. institutions of the EU the best-possible scientific advice on any question relating to the evaluation of the quality, • We value the contribution of our partners and stake- safety and efficacy of medicinal products for human or holders to our work. veterinary use referred to it in accordance with the • We assure continual improvement of our processes provisions of EU legislation relating to medicinal prod- and procedures, in accordance with recognised quality ucts. standards. • We adhere to high standards of professional and Principal activities personal integrity. Working with the Member States and the European • We communicate in an open, transparent manner Commission as partners in a European medicines with all of our partners, stakeholders and colleagues. network, the European Medicines Agency: • We promote the well-being, motivation and ongoing professional development of every member of the • provides independent, science-based recommenda- Agency. tions on the quality, safety and efficacy of medicines, and on more general issues relevant to public and animal health that involve medicines; • applies efficient and transparent evaluation proce- dures to help bring new medicines to the market by means of a single, EU-wide marketing authorisation granted by the European Commission; • implements measures for continuously supervising the quality, safety and efficacy of authorised medi- cines to ensure that their benefits outweigh their risks; • provides scientific advice and incentives to stimulate the development and improve the availability of innovative new medicines; • recommends safe limits for residues of veterinary medicines used in food-producing animals, for the establishment of maximum residue limits by the European Commission; • involves representatives of patients, healthcare professionals and other stakeholders in its work, to facilitate dialogue on issues of common interest; • publishes impartial and comprehensible information about medicines and their use; • develops best practice for medicines evaluation and supervision in Europe, and contributes alongside the Member States and the European Commission to the harmonisation of regulatory standards at the inter- national level. Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011 Third ESVAC report 15 October 2013 EMA/236501/2013 Veterinary Medicines Division Acknowledgements The members and the observers of the ESVAC ad hoc expert group Christina Greko, Cristina Muñoz Madero, Albert Meijering, Gérard Moulin, Lucie Pokludová, Renee Sheehan, Pierre-Alexandre Beloeil, Rosa Peran and Klaus Weist are acknowledged for providing valuable comments and scientific advice during the production of this report. Furthermore, Klemens Fuchs, Lionel Laurier, Jeroen Dewulf, Damyan Iliev, Lucie Pokludová, Marios Genakritis, Erik Jacobsen, Katrin Kurvits, Katariina Kivilahti-Mäntylä, Gérard Moulin, Ann Chevance, Claire Chauvin, Jürgen Wallmann, Inke Reimer, János Kovács, Katalin Mészárosné Árvai, Jóhann M. Lenharðsson, Jeremiah Gabriel Beechinor, Gavin Ryan, Alessandra Perrella, Gundega Mičule, Gatis Ozoliņš, Unge Zymantaite, Albert Meijering, Dorota Prokopiak, Maria Helena Ponte, Teresa Mafalda Flores, Anton Svetlin, Martina Péteryová, Judita Hederová, Rinaldo Zidar, Cristina Muñoz Madero, Kinfe Girma, Christina Greko, Renee Sheehan and Suzanne Eckford are acknowledged for providing data and valuable comments for the report. Cedric Mϋntener is thankfully acknowledged for providing the data for Switzerland. The European Medicines Agency staff members Kari Grave, Jordi Torren-Edo, Arno Muller, Kristine Ignate and David Mackay are gratefully acknowledged for the preparation of the report. Citation Suggested citation: European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption, 2013. 'Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011' (EMA/236501/2013). Correspondence Any correspondence relating to this report should be sent by e-mail to: [email protected] DISCLAIMER The views and positions expressed in this report do not necessarily represent in legal terms the official position of the European Medicines Agency. The European Medicines Agency assumes no responsibility or liability for any errors or inaccuracies that may appear. About the European Medicines Agency The European Medicines Agency is a decentralised body of the European Union (EU), located in London. Its main responsibility is the protection and promotion of public and animal health, through the evaluation and supervision of medicines for human and veterinary use. The Agency is responsible for the scientific evaluation of applications for European marketing authorisations for both human and veterinary medicines (centralised procedure). Under the centralised procedure, companies submit a single marketing-authorisation application to the Agency. Once granted by the European Commission, a centralised marketing authorisation is valid in all EU Member States and, after implementation at national level, in the EEA-EFTA states (Iceland, Liechtenstein and Norway). The Agency, with the help of its Committee for Medicinal Products for Veterinary Use (CVMP), its former Scientific Advisory Group on Antimicrobials (SAGAM) and the current Antimicrobials Working Party (AWP), has produced a strong body of scientific advice1 in relation to the use of antimicrobials and the risk of antimicrobial resistance, with the intention to promote the continued availability of effective antimicrobials for use in animals, while at the same time acting to minimise risks to animals or man arising from their use. The European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) project was launched by the Agency in September 2009, following a request from the European Commission to develop a harmonised approach to the collection and reporting of data on the use of antimicrobial agents in animals from the Member States. About the report This third ESVAC report presents data on the sales of veterinary antimicrobial agents from 25 EU/EEA countries, provided at package level according to a standardised protocol and template2. Data from Switzerland are included in Annex 9, as, due to confidentiality issues, data from Switzerland could not be delivered in accordance with the ESVAC data-collection form. This report has special emphasis on food-producing animals. It is generally agreed that it takes at least three to four years in order to establish a valid baseline for the data on sales of veterinary antimicrobial agents. Consequently, the data from countries that have collected such data for the first or even second time should be interpreted with due caution. It should be emphasised that the data presented in this report should not be used alone as a basis for setting management priorities, but should always be considered together with data from other sources. 1 Available from the Agency's website via: Home > Special topics > Antimicrobial resistance. 2 Available from the Agency's website via: Home > Regulatory > Veterinary medicines > Antimicrobial resistance > European Surveillance of Veterinary Antimicrobial Consumption. Table of contents Summary ....................................................................................................................9 Introduction .............................................................................................................12 1. Technical notes ...................................................................................................14 1.1. Veterinary antimicrobial agents included in the data sets ..........................................................14 1.2. Variables reported for each antimicrobial veterinary medicinal product .......................................14 1.3. Population correction unit .....................................................................................................15 1.4. Calculation of PCU ...............................................................................................................15 1.5. Animal species and categories included; selection of data sources .............................................15 1.6. Updates of the 2010 data .....................................................................................................16 1.7. Reporting of the data...........................................................................................................16 1.8. Summary of included data sources/types, by country ..............................................................16 2. Results ...............................................................................................................20 2.1. Population correction unit .....................................................................................................20 2.2. Overall sales of veterinary antimicrobial agents .......................................................................23 2.3. Population-corrected sales for food-producing animals, including horses, by pharmaceutical form ..24 2.4. Population-corrected sales for food-producing animals, including horses, by antimicrobial class .....26 2.4.1. Explanations for observed changes in sales and sales patterns, 2010–2011 ..............................32 2.4.2. Distribution of sales for the most-selling antimicrobial classes and the most important CIAs, by pharmaceutical form, aggregated by the 25 EU/EEA countries ................................................36 2.5. Distribution of sales for food-producing animals, including horses, by antimicrobial class and pharmaceutical form for 25 countries .....................................................................................39 2.5.1. Tetracyclines ....................................................................................................................40 2.5.2. Amphenicols ....................................................................................................................41 2.5.3. Penicillins ........................................................................................................................42 2.5.4. 1st- and 2nd-generation cephalosporins ..............................................................................43 2.5.5. 3rd- and 4th-generation cephalosporins ..............................................................................44 2.5.6. Sulfonamides ...................................................................................................................45 2.5.7. Trimethoprim ...................................................................................................................46 2.5.8. Macrolides .......................................................................................................................47 2.5.9. Lincosamides ...................................................................................................................48 2.5.10. Fluoroquinolones ..............................................................................................................49 2.5.11. Other quinolones ..............................................................................................................50 2.5.12. Aminoglycosides ..............................................................................................................51 2.5.13. Polymyxins ......................................................................................................................52 2.5.14. Pleuromutilins ..................................................................................................................53 2.6. Distribution of single- and multiple-ingredient products of veterinary antimicrobial agents ............54 2.7. Sales of tablets by veterinary antimicrobial class for companion animals ....................................57 3. Discussion ..........................................................................................................59 3.1. Materials and methods.........................................................................................................59 3.2. Results ..............................................................................................................................60 4. Concluding remarks ............................................................................................62 Annex 1. Tables ...............................................................................................................................63 Annex 2. Variables to be reported for each antimicrobial veterinary medicinal product; standardisation of the data .........................................................................................................................69 Annex 3. Population correction unit (PCU)............................................................................................72 Annex 4. List of antimicrobial classes/active ingredients reported in ESVAC ..............................................74 Annex 5. Distribution of veterinary medicines; legal framework and data sources by country ......................76 Annex 6. References to national reports ..............................................................................................87 Annex 7. Country and affiliation of the ESVAC national representatives/alternates .....................................88 Annex 8. ESVAC ad hoc Expert Group members and observers ...............................................................93 Annex 9. Data from Switzerland .........................................................................................................95 List of figures Figure 1. Organisation of the ESVAC project .........................................................................................13 Figure 2. PCU (in 1,000 tonnes) of the various food-producing animal species, including horses, by country, for 2011 and 2010 ..............................................................................................21 Figure 3. Distribution of PCU (1,000 tonnes), by food-producing animal species, including horses, by country, for 2011 ............................................................................................................22 Figure 4. Net export and net import, as a percentage of the total PCU, of animals for fattening or slaughter in another Member State, for 2011 ..........................................................................22 Figure 5. Distribution of sales, in tonnes of active ingredient, split into tablets (used almost solely in companion animals) and all other pharmaceutical forms (used mainly in food-producing animals, including horses), by country, for 2011 ..................................................................................24 Figure 6. Distribution of sales of veterinary antimicrobial agents for food-producing animals (including horses), in mg per population correction unit (mg/PCU), by pharmaceutical form, by country, for 2011 ............................................................................................................................24 Figure 7. Oral solutions, oral powders and premixes as percentages of total sales, in mg per population correction unit (mg/PCU), of veterinary antimicrobial agents for food-producing animals (including horses), by country, for 2011 .................................................................................25 Figure 8. Distribution of sales, in mg/PCU, of the various pharmaceutical forms of veterinary antimicrobial agents for food-producing animals (including horses) aggregated by the 25 EU/EEA countries for 2011 ............................................................................................................................25 Figure 9. Sales for food-producing species, including horses, in mg/PCU, of the various veterinary antimicrobial classes, by country, for 25 countries in 2011 and for 20 countries in 2010 ...............28 Figure 10. Proportion of the total sales of the different veterinary antimicrobial classes, in mg/PCU, by country, for 2011 ............................................................................................................29 Figure 11. Sales of antimicrobial agents by antimicrobial class as a percentage of the total sales for food- producing species (including horses), in mg/PCU, aggregated by the 25 countries, for 2011 ..........29 Figure 12. Sales of tetracyclines, penicillins and sulfonamides as a percentage of the total sales for food- producing species (including horses), in mg/PCU, by country, for 2010 and 2011 .........................30 Figure 13. Distribution of sales in mg/PCU of penicillins, by subclass, for food-producing species, including horses, by country, for 2011 ...................................................................................30 Figure 14. Percentages of the total sales of macrolides, fluoroquinolones and 3rd- and 4th-generation cephalosporins for food-producing species, including horses, in mg/PCU, by country, for 25 countries in 2011 and 20 countries in 2010 ...................................................................31 Figure 15. Distribution of sales of tetracyclines for food-producing animals (including horses), in mg/PCU, by the major pharmaceutical forms sold, aggregated by the 25 EU/EEA countries for 2011 ...........36 Figure 16. Distribution of sales of penicillins for food-producing animals (including horses), in mg/PCU, by the major pharmaceutical forms sold, aggregated by the 25 EU/EEA countries for 2011 ...........37 Figure 17. Distribution of sales of sulfonamides for food-producing animals (including horses), in mg/PCU, by the major pharmaceutical forms sold, aggregated by the 25 EU/EEA countries for 2011 ...........37 Figure 18. Distribution of sales of 3rd- and 4th-generation cephalosporins for food-producing animals (including horses), in mg/PCU, by pharmaceutical form sold, aggregated by the 25 EU/EEA countries for 2011 ...............................................................................................................38 Figure 19. Distribution of sales of macrolides for food-producing animals (including horses), in mg/PCU, by pharmaceutical form sold, aggregated by the 25 EU/EEA countries for 2011 ...........................38 Figure 20. Distribution of sales of fluoroquinolones for food-producing animals (including horses), in mg/PCU, by the major pharmaceutical forms sold, aggregated by the 25 EU/EEA countries for 2011 ............................................................................................................................39 Figure 21. Spatial distribution of sales of tetracyclines for food-producing animals, in mg/PCU, in 25 EU/EEA countries, for 2011 ..........................................................................................40 Figure 22. Distribution of sales by pharmaceutical form for tetracyclines, in mg/PCU, by country, for 2011 .....40 Figure 23. Spatial distribution of sales of amphenicols, in mg/PCU, in 25 EU/EEA countries, for 2011 ............41 Figure 24. Distribution of sales by pharmaceutical form for amphenicols, in mg/PCU, by country, for 2011 .....41 Figure 25. Spatial distribution of sales of penicillins for food-producing animals, in mg/PCU, in 25 EU/EEA countries, for 2011 ..............................................................................................................42 Figure 26. Distribution of sales by pharmaceutical form for penicillins, in mg/PCU, by country, for 2011 .........42 Figure 27. Spatial distribution of sales of 1st- and 2nd-generation cephalosporins, in mg/PCU, in 25 EU/EEA countries, for 2011 ..........................................................................................43 Figure 28. Distribution of sales by pharmaceutical form for 1st- and 2nd-generation cephalosporins, in mg/PCU, by country, for 2011 ...........................................................................................43 Figure 29. Spatial distribution of sales of 3rd- and 4th-generation cephalosporins, in mg/PCU, in 25 EU/EEA countries, for 2011 ..........................................................................................44 Figure 30. Distribution of sales by pharmaceutical form for 3rd- and 4th-generation cephalosporins, in mg/PCU, by country, for 2011 ...........................................................................................44 Figure 31. Spatial distribution of sales of sulfonamides, in mg/PCU, in 25 EU/EEA countries, for 2011 ...........45 Figure 32. Distribution of sales by pharmaceutical form for sulfonamides, in mg/PCU, by country, for 2011 ....45 Figure 33. Spatial distribution of sales of trimethoprim, in mg/PCU, in 25 EU/EEA countries, for 2011 ...........46 Figure 34. Distribution of sales by pharmaceutical form for trimethoprim, in mg/PCU, by country, for 2011 ....46 Figure 35. Spatial distribution of sales of macrolides, in mg/PCU, in 25 EU/EEA countries, for 2011 ...............47 Figure 36. Distribution of sales by pharmaceutical form for macrolides, in mg/PCU, by country, for 2011 .......47 Figure 37. Spatial distribution of sales of lincosamides, in mg/PCU, in 25 EU/EEA countries, for 2011 ............48 Figure 38. Distribution of sales by pharmaceutical form for lincosamides, in mg/PCU, by country, for 2011 ....48 Figure 39. Spatial distribution of sales of fluoroquinolones, in mg/PCU, in 25 EU/EEA countries, for 2011 .......49 Figure 40. Distribution of sales by pharmaceutical form for fluoroquinolones, in mg/PCU, by country, for 2011 ............................................................................................................................49 Figure 41. Spatial distribution of sales of other quinolones, in mg/PCU, in 25 EU/EEA countries, for 2011.......50 Figure 42. Distribution of sales by pharmaceutical form for other quinolones, in mg/PCU, by country, for 2011 ............................................................................................................................50 Figure 43. Spatial distribution of sales of aminoglycosides, in mg/PCU, in 25 EU/EEA countries, for 2011 .......51 Figure 44. Distribution of sales by pharmaceutical form for aminoglycosides, in mg/PCU, by country, for 2011 ............................................................................................................................51 Figure 45. Spatial distribution of sales of polymyxins, in mg/PCU, in 25 EU/EEA countries, for 2011 ..............52 Figure 46. Distribution of sales by pharmaceutical form for polymyxins, in mg/PCU, by country, for 2011 ......52 Figure 47. Spatial distribution of sales of pleuromutilins, in mg/PCU, in 25 EU/EEA countries, for 2011 ..........53 Figure 48. Distribution of sales by pharmaceutical form for pleuromutilins, in mg/PCU, by country, for 2011 ..53 Figure 49. Percentage of sales, in tonnes of active ingredient, of premixes, oral powders and oral solutions containing 1, 2 and 3 antimicrobial agents .............................................................................57 Figure 50. Distribution of sales of tablets, in tonnes of active ingredient, by antimicrobial class (reported according to the ATCvet hierarchical system), by country, for 2011 ............................................58 Figure 51. Distribution of sales of tablets containing penicillins, by subclass, (in weight of active ingredient), by country, for 2011 ...........................................................................................58 List of tables Tables in the main text Table 1. Categories and ATCvet codes of antimicrobial veterinary medicinal products included in the data ...14 Table 2. Summary of information on years collecting data, legal basis for collecting data at national level, national data providers, sources for ESVAC data and characteristics of data by country for 2011....17 Table 3. Estimated PCU (in 1,000 tonnes) of the population of food-producing species (including horses), by country, for 2011 ............................................................................................................20 Table 4. Distribution of overall sales, in tonnes of active ingredient, split into tablets (used in companion animals) and all other pharmaceutical forms (used mainly in food-producing animals, including horses), by country, for 2011 ...............................................................................................23 Table 5. Sales, in tonnes of active ingredient, of veterinary antimicrobial agents marketed mainly for food-producing animals (including horses), population correction unit (PCU) and sales in mg/PCU, by country, for 2010 and 2011 ..............................................................................................26 Table 6. Percentages of sales for food-producing animals (including horses), in mg per population correction unit (mg/PCU), of the various veterinary antimicrobial classes, by country, for 2011 .....27 Table 7. Number of product presentations (product name, form, strength and pack size) containing 1, 2 and 3 antimicrobial agents, by country, for 2011 (tablets excluded from the data) .................54 Table 8. Number of product presentations (product name, form, strength and pack size) for premixes, oral powders and oral solutions containing 1, 2 and 3 antimicrobial agents, by country, for 2011 ...55 Table 9. Sales, in tonnes of active ingredient, of antimicrobial agents as premixes, oral powders and oral solutions containing 1, 2 and 3 active ingredients, by country, for 2011 ...............................56 Tables in Annexes 1-5 Table A1. Sales, in tonnes of active ingredient, of veterinary antimicrobial agents applicable mainly for food-producing animals, including horses, by antimicrobial class (presented according to ATCvet hierarchical system), by country, for 2011 (Tablets not included) ....................................63 Table A2. Distribution of sales, in mg/PCU, of veterinary antimicrobial agents applicable mainly for food-producing animals, including horses, by administration route/form and country for 2011 .......64 Table A3. Percentage of sales, in mg/PCU, of premixes by veterinary antimicrobial class (according to ATCvet system) by country for 2011 ......................................................................................65 Table A4. Percentage of sales, in mg/PCU, of oral powders by antimicrobial class (according to ATCvet system) by country for 2011 ......................................................................................66 Table A5. Percentage of sales, in mg/PCU, of oral solutions by antimicrobial class (according to ATCvet system) by country for 2011 ......................................................................................67 Table A6. Percentage of sales, in mg/PCU, of injection preparations by antimicrobial class (according to ATCvet system) by country, for 2011 .....................................................................................68 Table A7. Variables reported to ESVAC for each antimicrobial veterinary medicinal product for 2011 ............69 Table A8. Conversion factors used to convert from international units (IU) to weight (mg) of active ingredient based on WHO standards ......................................................................................71 Table A9. Conversion factors used to convert from prodrug content to content of active ingredient ..............71 Table A10. Animal categories included in the calculation of the population correction unit (PCU) and data types to be reported .....................................................................................................72 Table A11. Weights used to calculate the population correction unit ...........................................................73 Table A12. List of substances reported sold in ESVAC ..............................................................................74 Table A13. List of ESVAC national representatives/alternates ....................................................................88 Table A14. List of ESVAC ad hoc Expert Group members from EU Member States ........................................93 Table A15. List of ESVAC ad hoc Expert Group observers from the European Commission, ECDC and EFSA .....94 Summary A total of 26 European Union (EU)/European Economic Area (EEA) countries submitted to the European Medicines Agency their 2011 data on sales, at package level, of antimicrobial veterinary medicinal products (VMPs), according to a standardised protocol and using a common template. Greece could not validate its data, due to lack of resources, and these data were therefore not included in the report. The 25 countries included in the ESVAC 2011 data cover approximately 95% of the food-producing animal population in the EU/EEA area. For four countries, 2011 was the first year for which they had collected data on antimicrobial VMPs; nine countries had collected such data for 2 years, two countries for 3 years and ten countries for more than 5 years. Fifteen of the countries obtained the data from wholesalers, six from marketing-authorisation holders, two from both wholesalers and marketing-authorisation holders, and two from pharmacies. In some countries, feed mills provided the data on sales of premixes used in medicated feed. In 21 of the 25 countries, a legal basis existed for the national competent authority to request data on sales or prescription of veterinary antimicrobial agents from the distributors of such products, while in four countries (Ireland, France, the Netherlands and Spain), data were provided to the national competent authority voluntarily. All countries provided sales data or prescription data (Denmark and Sweden), except for two countries that provided purchase data (Hungary for 2010; Slovakia for 2011). For Hungary, the 2010 data represent imports by wholesalers, while the 2011 data represent sales from wholesalers to end-users; for Slovakia, 2011 data represent imports by wholesalers. Since wholesalers may not sell all the veterinary antimicrobial products the same year as they are imported, sales data for Hungary for 2010 are likely to be overestimated compared to the 2011 data. Similarly, the 2011 data for Slovakia are not likely to be fully comparable with those of the other countries. In order to normalise the sales data for the animal population that could be subjected to treatment with antimicrobial agents, a population correction unit (PCU) was introduced as a proxy for the size of the animal population. Since statistics on numbers of dogs and cats were not available from all countries, these species were not included in the PCU, and therefore tablets, which are almost solely used in companion animals, were excluded from the further analysis of the sales data and the PCU data. Injectable veterinary antimicrobial agents are used in both food-producing and companion animals. Due to the relatively small proportion used in companion animals, in terms of weight of active ingredient, sales of injectable preparations are included in the statistics for food-producing animals. The national sales data for antimicrobial agents (nominator) cover all food-producing species, including horses, thus the animal population 'at risk' of being treated with antimicrobial agents (denominator) includes all food-producing species. However, the use of antimicrobial agents in the various animal species varies considerably; for example, the use of antimicrobial agents in sheep and goats is relatively low, due to extensive production systems. Therefore, the interpretation of the data should take into account the distribution of the PCU value between the species in the various countries. It should also be emphasised that the PCU only represents a technical unit of measurement and not a real value for the animal population that could potentially be treated with antimicrobial agents. The main indicator used in the current report to express the sales is mg active ingredient sold per population correction unit (mg/PCU). Overall in the 25 countries, approximately 36% of the sales of veterinary antimicrobial agents, in mg/PCU, were for pharmaceutical forms applicable for mass treatment (i.e. premixes) and 56% for forms applicable for group treatment — i.e. oral powders (48%) and oral solutions (8%). The amount accounted for by these three pharmaceutical forms varied considerably between the countries. The proportion of the sales, in tonnes of active ingredient, of antimicrobial VMPs sold as injectable preparations was 7%, and 1% was for local uses (intramammary and intrauterine preparations). The distribution of sales of the various antimicrobial classes and subclasses by pharmaceutical form varied considerably between the 25 countries. Overall for the 25 countries, 43% of tetracyclines were sold as premixes, 51% as oral powders, 4% as oral solutions and 2% as injectable preparations. For penicillins, premixes accounted for 22%, oral powder for 63%, oral solutions for 2% and injections for 12% of the total sales in the 25 countries. For sulfonamides, premixes accounted for 38%, oral powders for 39%, oral solutions for 18% and injections for 4% in the 25 countries. Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011 Third ESVAC report 9 Of the sales (in mg/PCU) of 3rd- and 4th-generation cephalosporin preparations, none of the pharmaceutical forms was applicable for group treatment; 83% were injectable preparations and 17% were intramammary preparations. The proportion of fluoroquinolones sold as oral solution was 76% and injections accounted for 24% of the sales aggregated by the 25 countries. Premixes accounted for 33% of the total sales of macrolides in the 25 countries, oral powders for 53%, oral solutions for 8% and injectable preparations for 6%. Nineteen of the 20 countries that provided sales data to ESVAC in both 2010 and 2011 reported a decrease in sales (range 0.4%–28%) expressed as mg/PCU. For one country, an increase of 3.5% was reported from 2010 to 2011. However, one marketing-authorisation holder failed to report the sales data in 2010; for this company, the reported sales were 21% of the total sales in 2011; provided that the sales for this company were at the same level in 2010, the sales of veterinary antimicrobial agents have actually declined considerably. Overall in the 25 countries, 16% of the decline in the sales of veterinary antimicrobials from 2010 to 2011 was accounted for by premixes, 7% by oral powders and 4% by oral solutions. Suggested explanations provided by the countries for the decline in sales are, among others, implementation of responsible-use campaigns, restrictions of use, increased awareness of the threat of antimicrobial resistance, and/or the setting of targets. Additional detailed information on national programmes and campaigns on the responsible use of antimicrobial agents is needed before conclusions can be drawn on the efficacy of these campaigns in reducing the sales of antimicrobial agents. At the European level, this would provide data for interventions aimed at best practices for the use of antimicrobial agents in animals. A large difference in the sales, expressed as mg/PCU, is observed between the most- and least-selling countries (range 3.7–408 mg/PCU). This is in part likely to be due to differences in the composition of the animal population in the various countries (e.g. more pigs than cattle, or a high proportion of veal calves within the cattle population). There may also be considerable variation in terms of daily dose used for the various antimicrobial agents, length of treatment period, or formulations used; this may also in part explain some of the differences between the countries. However, these factors can only partly explain the differences in the sales observed between the 25 countries; other factors also need to be considered. Also, differences in the selection of data source may have an impact, but this is considered to be low. Of the overall sales in the 25 countries, the largest proportions, expressed as mg/PCU, were accounted for by tetracyclines (37%), penicillins (23%), sulfonamides (11%) and polymyxins (7%). For the antimicrobial classes belonging to the World Health Organization (WHO) list of critically important antimicrobials (CIAs) with highest priority in human medicine, namely 3rd- and 4th-generation cephalosporins, fluoroquinolones and macrolides, the sales for food-producing animals, including horses, accounted for 0.2%, 1.6% and 8%, respectively, of the total sales in the 25 countries in 2011. The prescribing patterns of the various antimicrobial classes, expressed as mg/PCU, varied substantially between the countries. Notable variations between the countries in the proportion of 3rd- and 4th-generation cephalosporins, fluoroquinolones and macrolides sold were observed, with sales ranging from 0.05% to 0.78%, 0.01% to 13.8% and 0% to 14%, respectively. The variations in prescribing patterns may be due to, for example, differences between countries in the veterinarians' prescribing behaviour, the relative proportion of the various animal species, animal-production systems (e.g. veal as opposed to beef cattle on pasture), the availability of veterinary antibacterial products on the market, prices, or the general situation with regard to infectious diseases. These factors only partly explain the differences in the sales patterns between the countries. Of the total numbers of product presentations of antimicrobial VMPs applicable for food-producing animals (including horses) — i.e. product name, pharmaceutical form, strength and pack size (tablets not included) — 81% contained only one active ingredient, 17% contained two active ingredients, 2% contained three active ingredients and 0.2% contained four active ingredients (these were intramammaries). Overall in the 25 countries, the proportion of the sales in 2011 of antimicrobial VMPs as premixes (for mass treatment), oral powders and oral solutions applicable for group treatment containing two or more active ingredients was relatively low. Of the total sales, 85%, 15% and 0.2% of these pharmaceutical forms contained one, two and three active ingredients, respectively. However, as it is possible to mix more than one premix/oral powder and oral solution into feed or drinking water, respectively, these data do not provide a reliable estimate of treatment through feed or drinking water with two or more active ingredients. Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011 10 Third ESVAC report