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

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.