Methods
How is the consumption of antibiotics measured?
The World Health Organization Collaborating Center for Drug Statistics Methodology defined the DDD (defined daily dose, DDD) as the assumed mean daily maintenance dose for a main indication of a drug in adults [1]. The DDD does not correspond to a recommended or actually prescribed daily dose, but to a technical unit of measure and comparison which has been assigned to each antibiotic.
Prescribed quantities of antibiotics are converted from grams into DDD and then reported for the inpatient sector as DDD per 100 days of care or as DDD per 1000 inhabitants per day (consumption density) for the outpatient sector respectively. This procedure is recommended by the WHO for comparative antibiotic consumption studies [2, 3, 4]. The number of inpatient days is defined by the Federal Statistical Office as the yearly sum of days on which patients stay in the stationary care.
- [1] World Health Organization Collaboration Center for Drug Statistics Methodology. ATC index with DDDs. Oslo : World Health Organization, 2005.
- [2] Dukes MN. Drug utilization studies. Methods and uses. WHO Reg Publ Eur Ser. 1993 ; 45 :1-4.
- [3] European Centre for Disease Prevention and Control. Antimicrobial consumption. In: ECDC. Annual Epidemiological Report for 2016. Downloadable tables. Stockholm: ECDC; 2018. Available from: European Centre for Disease Prevention and Control – Antimicrobial consumption – Annual Epidemiological Report for 2016
- [4] de With K, Maier L, Steib-Bauert M, Kern P, Kern WV. Trends in antibiotic use at a university hospital: defined or prescribed daily dose? Patient days or admissions as denominator? Infection. 2006; 34(2): 91-4.
Human Medicine – Hospital Sector
ANRESIS has established a voluntary monitoring network for Swiss acute care hospitals. Their hospital pharmacies send quantitative data to ANRESIS, both globally and stratified by ICU, pediatrics, and occasionally for other departments. The Swiss surveillance system includes about seventy hospitals, representing coverage of about 70% of bed days in acute care hospitals. Specialty hospitals, such as psychiatric hospitals or rehabilitation/geriatric hospitals, are not part of the surveillance network.
Human medicine – outpatient sector
Antibiotic consumption in the outpatient sector is monitored using two data sources: (i) IQVIA™, a private market research company, provides data on antibiotic sales from the pharmaceutical industry to pharmacies and self-dispensing physicians (IQVIA™ channels: APO/SD), (ii) PharmaSuisse provides data based on antibiotic prescriptions at the individual level from privately managed pharmacies through the Professional Association of Swiss Pharmacists (OFAC, Geneva). Data are from antibiotics dispensed by prescription in public pharmacies and billed to health insurers. Coverage was 50% of all pharmacies in Switzerland in 2021 (2020: 52%, 2019: 53%). Data were grouped by age category (<2 years; 2-11 years; 12-17 years; 18-64 years; >65 years). Relative consumption was measured by quantity in DDD.
Sales data
MAHs regularly report the sales figures for their products to IS ABV. Products that are solely licensed for export are excluded. Because they are not used in Switzerland, they do not contribute to the development of resistance in Switzerland.
Each product is entered in the IS ABV with a unique identification number, brand name, ATCvet code, target species and information on the approved method of application. Pharmaceutical premixes are listed separately. The entry also includes the number of “basic units” sold (e.g. vials [incl. volume], tablets, injectors, tubes or bags [incl. weight]).
The total quantities are then calculated by repeatedly multiplying the volume of active ingredient in each basic unit by the number of basic units sold. Combinable filters (year, ATCvet code, administration route) are used for specific queries. The quantity of active ingredient is recorded for each product and each basic unit. In the case of antibiotics expressed in international units, conversion factors are used according to the template provided by the European Surveillance of Veterinary Antimicrobial Consumption Project (ESVAC) of the European Medicines Agency [2]. Each MAH reviews and approves its data, which are summarised by preparation and year. Finally, the data are checked by Swissmedic before publication.
The methods of application were chosen in line with those used in similar reports in other countries (France, AFSSA and United Kingdom, VMD): oral, parenteral, intra-mammary and topical/external. The only distinction possible is that between “livestock”, “companion animals” and “mixed” according to the authorisations. Specific animal species or age groups could be covered only if clearly mentioned in the marketing authorisation (e.g. intra-mammary injectors for cows or products for treating piglets).
IS ABV
The Informationssystem für Antibiotika in der Veterinärmedizin (IS ABV) is a system for recording antibiotic prescriptions for animals. Since October 2019, veterinarians are required to report all antibiotic prescriptions and sales for all animal species. The database allows the intensity of treatment of farm animals and companion animals to be assessed. It also takes into account the different types of production, e.g. piglet rearing or dairy farming. The system will also allow regional, national and international comparisons of antibiotic consumption and treatment intensity.
For the veterinary profession, mandatory reporting of antibiotic prescriptions in the IS ABV database can be done via the practice software or a local IS ABV app. Group therapies can be reported only via the local IS ABV app. For veterinarians, reporting via the practice software has the advantage that prescriptions only need to be recorded once, in the veterinary practice or clinic. For the evaluation, however, it also means that two reporting channels need to be taken into account, which is a potential source of error. Most veterinary practices and clinics use the reporting channel via the practice software.
It was also found that it is essential for reporting veterinarians to be able to check their prescription reports stored on the IS ABV server. Regular feedback of data submitted by practices has been in place since May 2021. The quality of the data is continuously updated via monthly feedback to veterinarians and constant access by farmers to their personal consumption data. Only veterinarians can update their own data in the IS ABV software. Improvements in error rates have been observed since this feedback was introduced.
Ultimately, the responsibility for correct reporting to IS ABV lies with the veterinarian. IS ABV is continually being improved in order to make the reporting of prescriptions as easy as possible.
A three-step data cleansing process has been introduced to identify and then exclude outliers. The first and second exclusion criteria are based on the median of the declared quantity per day and animal per antimicrobial class, as well as on the preparation and the production group. Prescriptions with a given quantity per day per animal above 15 times the median and/or the 99th percentile were excluded. Finally, all prescriptions were checked manually using the “four eyes” principle to exclude any obvious errors in the database. The data cleansing concerned only penicillins, tetracyclines and sulfonamides. In total, 6,557 prescriptions (0.8 % of all prescriptions) were excluded from the active ingredient quantity analyses. This procedure was not possible for the prescription type “issued from stock”, as neither the use category nor the number of animals treated had to be recorded.