Animal defined daily dosages
The defined daily dose animal (DDDA) is the unit of measurement for the determination of annual veterinary antimicrobial drug consumption. In the Netherlands, DDDA’s are derived from Dutch AVMP authorization documents and we will refer to this parameter as the DDDANL. The DDDANL is established per AVMP and species and represents the amount of AVMP (in g or mL or pieces) needed for the treatment of one kg of animal for one day in accordance to the mean authorized dosage for the target animal. The DDDANL for AVMPs with a prolonged duration of action (i.e. more than 24 h) or a shorter duration of action (applied 2 times daily) are corrected for this by a correction factor either retrieved from the authorization documents or based on expert consensus within the SDa. Full details on DDDANL definition as well as data collection, exact contents of datasets, and calculation of the total veterinary antimicrobial consumption in livestock were published previously [16, 17].
A comparable parameter for calculation of annual antimicrobial drug consumption is referred to as Animal Daily Dose (ADDDK). The ADDDK is the assumed average maintenance dose needed to treat one kg of animal during one day for the main indication in the target species in accordance with the Danish authorization document of the specific AVMP [13, 18]. The ADDDK was applied as the unit of measurement in DANMAP 2009–2011. In the provided data for this study the ADDDK was expressed as the amount of an AVMP (in g or mL or pieces) needed per kg animal per day.
The third applied animal defined daily dosages are the Defined Animal Daily Dose (DADDDK) as reported since DANMAP 2012 [19]. The DADDDK is specified per animal species and is a standardized dose in mg/kg per day for the main indication of a given active ingredient and a specified route of administration and pharmaceutical form. For orally administered antimicrobials, a differentiation is made between types of formulations, for example premixed feed or soluble powder for drinking water medication. For some parenterally administered active compounds a differentiation is made between immediate release preparations and those with prolonged effect [20]. Thus, the DADDDK is a measure established at the level of the active ingredient, route of administration and pharmaceutical form and not at the level of a specific AVMP, which are the main differences between the establishment of this unit of measurement and the ADDDK and DDDANL.
Data collection
Data on deliveries of AVMPs to individual farms for the complete Dutch pig sector from the year 2012 were collected by the quality assurance organisations of the Dutch pig sector, and provided to the Netherlands Veterinary Medicines Authority (SDa) for the monitoring of antimicrobial consumption in livestock. Numbers of animals per farm specified by subcategory (production animals or finisher pigs) and farm types (sows/piglets or finisher pigs) were incorporated in this dataset. Farms that used a closed system housing both sows/piglets and finisher pigs were divided in a sows/piglet farm and a finisher pigs farm. Individual farms were recognizable by an unique number but the encryption key was not available to the researchers, ensuring anonymous analysis of the data.
The SDa provided the database with the DDDANL per AVMP originally used to process the Dutch pig data of 2012 (version May 2013). A recent list of DDDANL is publicly available on the SDa website [21]. The Danish ADDDK used in this study were provided by the Danish Ministry of Food, Agriculture and Fisheries. The DADDDK per active compound defined for pigs was retrieved from the DADD description annex of DANMAP 2012 [20] and entered manually into a worksheet.
Data analysis
All different AVMPs, identifiable by European Article Number (EAN), delivered to pig farms in the Netherlands in 2012 were derived from the dataset provided by the SDa. Using the ADDDK list from the Danish ministry of Food, Agriculture and Fisheries, Danish equivalent products were selected for each Dutch product. The criteria used in the selection process are shown in Fig. 1. For some products no Danish equivalent could be established, as no products with certain combinations of active compounds or with a certain administration route are authorized in Denmark. Following assessment of the impact of deletion of these records on the number of DDDANL/Y, the delivery records for these products were excluded from all analyses.
Since 2013 the SDa reports the veterinary antimicrobial consumption in livestock as Defined Daily Dosages Animal per year on national level, expressed in this study as the number of DDDANL/Y (identical to the Dutch acronym DDDANAT, but expressed differently here to improve readability of this paper). The total amount of packages including package size (identifiable by EAN) delivered per year per farm type/animal category (sows/piglets or finisher pigs) and the mean numbers of animals at risk per farm type per day were derived from the data provided by the SDa. The standardized animal weights were established by the SDa together with representatives from the Dutch pig sector. The standardized animal weights applied in all analyses in this study are: sows/piglets 303.8 kg (=1 sow (220 kg) + 5.5 piglets (12.5 kg each) + 0.14 gilts (107.5 kg)) and finisher pigs 70 kg.
Using the DDDANL, the delivery records and the package size using the EAN-code, the total amount of kilograms of target animal that can be treated for one day per package of AVMP can be determined. This amount is referred to as amount of treatable kilograms*days. The total amount of treatable kg*days were calculated per animal (sub) category (also referred to as farm type). By dividing this amount with the standardized animal weight for the animal category, the total treatable number of animals*days based on the deliveries was calculated. The number of DDDANL/Y was then calculated per farm type by dividing the total amount of treatable animals*days by the total of animals at risk per day per farm type. The same process was repeated to calculate the number of ADDDK/Y and number of DADDDK/Y.
Differences between the animal defined daily dosages DDDANL, ADDDK and DADDDK as units of measurement were analysed on a more detailed level by determining the total amounts of treatment days per therapeutic group of AVMPs (as defined by the SDa, based on the ATCvet classification established by the World Health Organization). Sows/piglet farms and finisher pigs farm were analysed separately.
All analyses were performed using SAS® software version 9.2 (SAS institute Inc., Cary, NC, USA).