Good quality data are essential to better understand the relationship between antibiotic resistance and use. Manufacturers, marketing authorization holders (depositors), and drug wholesalers must report the distribution of veterinary drugs containing antimicrobial substances. In addition, veterinarians running home pharmacies report the quantities of antibiotics dispensed to farms. The legal basis for the collection of these data is the Veterinary Antibiotics Flow Regulation. In this report, the distribution and dispensing quantities of antibiotics approved for use in veterinary medicine for farm animals in 2022 are presented and compared with previous years. The total sales volume of antimicrobials for livestock decreased by 12.3% compared to the previous year and is 34.26 tons in 2022. The sales volume of antibiotics classified by the WHO as "antibiotics of the very highest importance for human medicine" has decreased by 6% since the previous year, from 4.64 to 4.35 tons. Over the years, these groups of active ingredients have accounted for a relatively constant share of around 12% of the total volume. In general, the sales volumes of recent years show fluctuations, which on the one hand have to do with the availability of some veterinary specialties and on the other hand can be attributed to the build-up and reduction of inventories. The underlying animal population shows only minor fluctuations over the last years, therefore changes in the sales volume cannot be attributed to lower or higher animal numbers. Veterinarians in charge of in-house pharmacies indicate the animal species for which the antibiotic was dispensed in their dispensing reports. This makes it possible to allocate the quantities of antimicrobial substances dispensed to the animal species. In order to be able to compare the quantities dispensed for the different animal species, these must be standardized on the basis of the respective animal population. For this purpose, the European Medicines Agency (EMA) has introduced a normalization factor (the PCU). The PCU is a technical measurement and refers to one kilogram of body weight. This results in normalized values for pigs of 53.3 mg/PCU (-7.3 mg/PCU compared to the previous year), cattle of 16.8 mg/PCU (no change compared to the previous year) and poultry of 18.7 mg/PCU (-3.3 mg/PCU). Since no directly applied antibiotics are recorded as part of the dispensing survey, these figures are subject to greater uncertainty.

The Veterinary Antibiotics Flow Regulation (BGBl. II No. 83/2014, last amended by BGBl. II No. 127/2022) provides the legal basis for a system to record the distribution and consumption of antibiotics in the veterinary sector in Austria. According to §4(2), AGES has the task to prepare a report on the evaluation of the data and to publish it via the Federal Ministry of Social Affairs, Health, Care and Consumer Protection.

In this report, the distribution volumes of antibiotics that were approved in veterinary medicine for farm animals in the years 2018 to 2022 and the dispensing volumes of the years 2018 to 2022 are presented.

For the years 2010-2013, the sales volumes of veterinary medicinal products containing antibiotics were reported electronically to AGES by the manufacturers, marketing authorization holders (depositors) and pharmaceutical wholesalers via a document specified by the EMA (European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption 2021) and prepared by AGES. With the entry into force of the Veterinary Antibiotics Flow Regulation, a new system was introduced for the first time for the collection of data for 2014; since then, manufacturers, marketing authorization holders (distributors) and pharmaceutical wholesalers have been uploading their data directly into the database via the homepage of the AGES Medical Market Authority. From this data, the total quantity of active ingredient sold is calculated in tons.

In addition, since 2016, veterinarians in charge of in-house pharmacies have had to upload their data on the dispensing of antibiotics for use on livestock (except horses, see Veterinary Antibiotics Flow Regulation §7(2)) for the respective previous year either independently or electronically via recognized reporting points in the new system in accordance with the Veterinary Antibiotics Flow Regulation (Veterinär-Antibiotika-MengenströmeVO). These data include, among other things, information on the type of animal and type of use. This makes it possible to allocate the quantity of antimicrobially active substances to individual animal species as of the data for 2015.

For the classification of active substances, the ATCvet system (World Health Organization Collaborating Centre for Drug Statistics Methodology, n.d.) is used in analogy to the ATC system used in human medicine. For antibiotics reported in international units, conversion factors have been provided by the EMA (European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption 2021). Antiparasitics with the ATCvet code "QP51AG" were not licensed in Austria during the evaluation period and therefore do not appear in the analyses.

Categories considered or associated ATCvet codes (World Health Organization Collaborating Centre for Drug Statistics Methodology, n.d.; European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption 2021).

Analyses were performed using the R programming language (R Core Team 2023).

Compared to 2021, there was a decrease of 4.81 tons in the total amount sold in 2022. This represents a relative decrease of 12.3%.

As before, antibiotics for systemic use (QJ01) are the most sold in terms of volume, accounting for over 90%. The following figure shows the quantity sold on the basis of the ATCvet code given in the expert information.

Looking at the type of application, oral preparations for the treatment of individual animals or groups of animals - these include powders, tablets and pastes - are far ahead of the other forms of application, with 27.2 tons (79.5%), even in 2022. Parenterally applied preparations are in second place with 5.3 tons (15.3%), followed by the group of intramammary applications, to which dry preparations were also assigned, with 1.04 tons (3%). The oral feed drug premixes (premix) used for stock treatment account for 0.63 tons (1.8%) in terms of volume.

In terms of sales volumes broken down by groups of active ingredients, tetracycline remains in first place with 15.8 metric tons (46.1%), followed by extended-spectrum penicillins with 5.9 metric tons (17.2%), sulfonamides with 3.2 metric tons (9.3%) and macrolides with 2.6 metric tons (7.6%). The classification of the active ingredients into active ingredient groups was carried out analogously to the specifications of the EMA (European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption 2021). The group "Other antibiotics" includes, among others, "Rifaximin" and "Spectinomycin".

Evaluations of the active ingredient groups of macrolides, fluoroquinolones, 3rd and 4th generation cephalosporins and polymyxins, which are classified by the WHO as antibiotics of utmost importance for human medicine, are also presented separately in the chapter "Antibiotics of utmost importance for human medicine".

Volumes sold by active ingredient group for the years 2018 to 2022 and the difference between the years 2022 and 2021 in metric tons.

For antibiotics for intestinal use (ATCvet QA07), there has been a decrease in the quantity sold in 2022 compared to 2021.

Volumes sold by active ingredient group (for intestinal use) for 2018 to 2022 and the difference between 2022 and 2021 in tons.

The following table shows the quantities of intramammary antibiotics (ATCvet QJ51) applied, broken down according to dryer and other preparations used during lactation. A slight increase compared to the previous year can be observed here.

Sold quantities by active ingredient group (for intramammary use) for the years 2018 to 2022 and the difference between the years 2022 and 2021 in tons.

The following two tables show the sales volumes of antibiotics for systemic use (ATCvet QJ01) by active ingredient group and application form. The greatest decrease can be seen in the tetracyclines. With regard to the form of application, a larger decrease is recorded for the orally administered antibiotics.

Volumes sold by active ingredient group (for systemic use) for the years 2018 to 2022 and the difference between the years 2022 and 2021 in tons.

Volumes sold by form of application (for systemic use) for the years 2018 to 2022 and the difference between the years 2022 and 2021 in tons.

The sales volumes of antibiotics for intrauterine use (ATCvet QG01, QG51) are shown per active ingredient group in the following table. These show a slight increase compared to the previous year only for tetracyclines.

Volumes sold by active ingredient group (for intrauterine use) for the years 2018 to 2022 and the difference between the years 2022 and 2021 in tons.

The active ingredient groups macrolides, fluoroquinolones, 3rd and 4th generation cephalosporins and also the group of polymyxins (including colistin) are classified by the WHO as so-called Highest Priority Critically Important Antimicrobials (HPCIA) due to their status (WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance and World Health Organization 2017). WHO also includes 5th generation cephalosporins, ketolides, and glycopeptides among HPCIA; however, these do not have sales volumes. The volumes of these groups of agents sold between 2018 and 2022 are shown in the following table and figure. There has been a decrease here, particularly in polymyxins, and an increase in macrolides compared to the previous year.

Sold quantities of antibiotics of very high importance for human medicine (HPCIA) for the years 2018 to 2022 and the difference between the years 2022 and 2021 in tons.

In addition to the WHO classification mentioned above, the EMA Antimicrobial Advice Ad Hoc Expert Group (AMEG) has made a new categorization of antimicrobial agents - based on potential public health consequences - into four groups (European Medicines Agency, Committee for Medicinal Products for Veterinary use (CVMP), Committee for Medicinal Products for Human Use (CHMP) 2019):

• Category A: Avoid - do not use in food-producing animals.
• Category B: Restrict - critically important for human medicine
• Category C: Caution - to be considered only unless clinically effective antibiotics from Category D are available
• Category D: Caution - to be used as first-line therapy when possible; only when needed.

The results of the sales volumes can be seen in the following figure, where group A does not occur in Austria.

In the previous chapters, the purely surveyed sales volumes were compared with each other over the last few years. No normalization was performed on the basis of the respective animals kept (animal populations per year). In the ESVAC reports, in order to take into account the different animal demographics of the countries, the Population Correction Unit (PCU) was defined, which is calculated from herd and slaughter data, as well as imports and exports. For more information on the calculation of the PCU, see Annex 3 of the report "Trends in the sales of veterinary antimicrobial agents in nine European countries: 2005-2009" (European Medicines Agency 2011).

The unit mg/PCU is a technical quantity used to compare quantities of different animal species, countries or years; 1 PCU = 1 kg. This normalization factor shows only minor fluctuations for Austria over the last few years. This means that the changes in quantities cannot generally be explained by higher or lower animal numbers in the respective years. In the following figure, the sales volumes are shown normalized on the basis of the PCU. Here, a reduction of 12.3% can be seen in 2022 compared to the previous year.

The distribution quantities presented so far exclusively include veterinary medicinal products that are approved for at least one farm animal species (or horses). Recently, all veterinary medicinal products with antimicrobial active ingredients have been reported in the distribution quantity report, including those that are only approved for pet animals (dogs, cats, etc.). The quantities in recent years are listed in the following table and range from 500 to 610 kilograms.

In Austria, 1776 HAPOs were registered in 2022, of which 1621 also purchased antibiotics in 2022, with 95% of antibiotics sold to 349 HAPOs (about 20%). Conversely, this means that 80% of HAPOs purchased only 5% of the total.

In the dispensing report, veterinarians in charge of in-house pharmacies must state which antibiotics were dispensed to which farms, and in what quantities. A total of 553 of 1776 HAPOs complied with this reporting obligation for the reporting year 2022.

In order to be able to check the completeness of the dispensing data, veterinarians in charge of in-house pharmacies who are not obliged to submit a dispensing report according to the Veterinary Antibiotics Flow Regulation §7(2) must submit an empty dispensing report (see Veterinary Antibiotics Flow Regulation §7(3)). This year, 873 HAPOs have carried out such a declaration.

Of the aforementioned 349 HAPOs (top 95%), 304 have made a delivery report or empty delivery report. In total, about 27.4 tons of antibiotics dispensed to farms were reported. The difference of about 6.9 tons (20%) to the reporting of manufacturers, depositors and drug wholesalers may have different reasons (e.g..: Use by veterinarian, dispensing to non-reportable species, stockpiling, non-reporting). The following table shows the dispensing and distribution quantities, as well as the respective differences and shares.

In addition to the information on which farms antibiotics were dispensed, the veterinarians in charge of in-house pharmacies must also report for which animal species and type of use the antibiotics were dispensed. In the following figure it can be seen that in 2022 67% of the quantity was dispensed for the animal species pig, followed by cattle with 27% and poultry with 6%.

The table shows the reported delivery quantities for pigs per active ingredient group in tons. A breakdown of the quantities dispensed for pigs by type of use is shown in the further table. This means, for example, that in 2022 a share of 26.6% of all dispensed antibiotics was used in pig fattening.

Dispensed quantities for the animal species pig per active ingredient group in tons for the years 2018 to 2022.

Percentage of total sales volume for the animal species swine per type of use for the years 2018 to 2022.

The table shows the reported release quantities for cattle per active ingredient group in metric tons, and the further table shows them as a percentage by type of use.

Percentage of total sales volume for cattle per type of use for 2018 to 2022.

The following table shows the reported release quantities for poultry per active ingredient group in tons. In analogy to previous chapters, the further table shows the release quantities in percent by type of use for poultry.

Release quantities for the animal species poultry per active ingredient group in tons for the years 2018 to 2022.

Percentage of total sales volume for poultry by type of use for 2018 to 2022.

• Left part of the graph Temporal development of the values of nDDvet per year of an example HAPO separated according to the three summarized active ingredient categories and overall. The classification of active substances into categories has been redefined based on the recently published report of the EMA (European Medicines Agency, Committee for Medicinal Products for Veterinary use (CVMP), Committee for Medicinal Products for Human Use (CHMP) 2019).
• Right part of graph Comparison of total nDDvet per year with nDDvet per year of all other veterinary family pharmacies for the current evaluation year. Here, the light gray area contains the HAPOs whose average nDDvet/year values are in the lower mean of all HAPOs (lower 50%). The dark gray area, on the other hand, contains the HAPOs whose average nDDvet/year values are in the upper 10%. The black check reflects the average nDDvet/year value of the example HAPO. If the dot is in the light gray area, this HAPO is one of the HAPOs with a low to medium average nDDDvet/year value. If it is in the dark gray area, this HAPO is among the 10% of HAPOs with the highest nDDvet/year values.

In the example shown, the average nDDvet/year value is 6.55, placing this HAPO among the 10% of HAPOs with the highest nDDvet/year values.

The large decline in sales volumes from the previous year continued this year, and at 34.26 metric tons is the lowest value since the start of data collection (for the first time for 2010). The last few years were also characterized by stronger fluctuations in sales volumes, which could be explained in part by inventory buildup or reduction (due to uncertainty about the market situation and the (non-)availability of drugs).

Sales volumes of agents classified as Highest Priority Critically Important Antimicrobials (HPCIA) (WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance and World Health Organization 2017) have fluctuated between 4.34 and 5.78 metric tons over the past five years, reaching 4.34 in 2022. Over the years, HPCIA have accounted for a relatively constant 12% to 13% of the total.

The mg/PCU indicator, which is a rough estimate of how many mg of antibiotics were sold per kg of live animal mass produced, decreased to 36.2 mg/PCU in 2022, which is 12.3% lower than in 2021. In absolute terms, this represents a decrease of 5.1 mg/PCU. The ratio of antibiotics purchased by HAPO in total to antibiotics dispensed in total was 79% in 2021 and 80.3% in 2022.

Based on the Austrian recording system, in which HAPOs must report their dispensing quantities per farm, animal species and type of use, it is possible to produce species-specific evaluations. The release quantities of the year 2022 show no change for the animal species cattle and a decrease for the animal species pig (-7.3 mg/PCU) and poultry (-3.3 mg/PCU) compared to the previous year. As mentioned, these values only reflect a trend and are subject to certain uncertainties.

With the "Animal Health Data Service" (AHDS), a new evaluation platform was created this year, which links different databases and provides targeted evaluations for the respective user groups. Cattle/pig farmers and veterinarians in charge of in-house pharmacies can already view their antibiotic evaluations via the AHDS. Easy access to these evaluations is intended to make a further contribution to raising awareness of antibiotic use.

Reinhard Fuchs ^DIin Elisabeth Reitbauer Univ.-Doz. DI Dr. Klemens Fuchs

Austrian Agency for Health and Food Safety GmbH Department of Integrative Risk Assessment, Data and Statistics Zinzendorfgasse 27, 8010 Graz With the kind support of AGES Medical Market Surveillance Division