Establishing defined daily doses (DDDs) for antimicrobial agents used for pigs, cattle and poultry in Japan and comparing them with European DDD values

Abstract

Monitoring of antimicrobial use is essential to manage the development and selection of antimicrobial resistance. A variety of indicators has become available to monitor antimicrobial use in human and animal medicine. One of them is an indicator based on defined daily dose (DDD). By using the number of DDDs used and normalizing it by the population at risk of being treated in a defined period, one can estimate the number of treatment days with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values of DDD (DDDvet) for food-producing animals. In this study, we defined Japanese defined daily doses for antimicrobial agents (DDDjp) using DDD values that we previously assigned for antimicrobial products approved for use in pigs, cattle and poultry in Japan and compared them with DDDvet values. For the comparison, the quotient of Japanese and European values (QDDD) was calculated and the effect of the administration route and the number of active substances contained in the preparation was investigated. A total of 59, 51 and 27 DDDjp values were defined for 43, 32 and 25 antimicrobial agents using the data of 269, 195 and 131 products approved for use in pigs, cattle and poultry respectively. A comparison was possible for 44, 27 and 17 pairs of DDDjp and DDDvet values for antimicrobial agents used for pigs, cattle and poultry respectively. The comparison showed median QDDD value of 0.66 and 0.63 for antimicrobial agents used for pigs and cattle respectively (P<0.01), indicating that the Japanese daily doses are significantly lower than the corresponding EMA values in these species. For the antimicrobial agents used for poultry, no siginificant difference was observed between DDDjp and DDDvet values with median QDDD value of 1.17. The difference between DDDvet and DDDjp values and absence of DDDvet values for some antimicrobial agents marketed in Japan indicate that DDDjp rather than DDDvet should be used as the basis for the calculation of antimicrobial use monitoring in farm animals in Japan.

Evaluating the antimicrobial use on dairy farms in Chiba Prefecture in Japan using the antimicrobial treatment incidence, an indicator based on Japanese defined daily doses from 2014–2016

“…This indicator presents a theoretical number of animals per 1000 animal-days subjected to antimicrobial treatment on the farm, assuming that the antimicrobial products are used in a cow of standard weight according to the dosage specified in the summary of product characteristics. To determine this indicator, we first calculated the number of DDDjps of antimicrobial agent (a) administered by route (r) on farm (i) in year (y) by dividing the weight of active ingredient of the antimicrobial agent (a), as follows: where the DDDjp value of the antimicrobial agent (a) administered by route (r) was available from the list of Japanese DDDjp values of antimicrobial agents established by Fujimoto et al [12]. In preparing this list, the DDDjp values for intramammary products for lactating cows and intrauterine products were assigned by dividing the daily dose per teat by 635 kg (standard weight of dairy cows assigned based on the average weight of dairy cows in 2014 in Japan [25]).…”

“…To establish a monitoring system using an indicator based on daily dosage in Japan, the DDD values (DDDjp) for veterinary antimicrobial agents used in antimicrobial products approved and marketed for use in cattle in Japan have been established recently [12].…”

“…DDDjp: DDD values assigned in mg/kg/day used in this study using DDD values of antimicrobial products approved and marketed for use in Japan[12] Distribution of the number of cows and antimicrobial treatment incidence (ATI) of the 442 dairy farms analyzed in this study Results of the regression analysis investigating the effect of administrative districts on the antimicrobial treatment incidence (ATI) #of the 442 dairy farms using a linear mixed-effect model with farm as random effect variable…”

Evaluation of antimicrobial use in dairy cattle, beef cattle and broilers in Japan using dosage-based indicators

“…To calculate the number of DDDs, we used the DDDjp values that we recently assigned for antimicrobial agents for use in pigs, cattle and poultry by active ingredient, administration route and number of active ingredients in the product (single substance and combination products) [6].…”

“…We have recently assigned DDDjp values for antimicrobial agents for use in cattle and poultry in Japan by active ingredient, administration route and number of active ingredients in the product [6].…”