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

Abstract

Monitoring of antimicrobial use is essential in the management of 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 administered and normalising it by the population at risk of being treated over 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 DDDjp values were defined for 43 antimicrobial agents using the data of 276 products approved for use in pigs. Likewise, a total of 55 DDDjp values were defined for 32 antimicrobial agents using the data of 196 products for use in cattle, and a total of 27 DDDjps values were defined for 25 antimicrobial agents using the data of 131 products approved for use in poultry. A comparison was made for 42, 28 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 0.61 and 0.66 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 significant difference was observed between DDDjp and DDDvet values with a median QDDD value of 1.15. 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.

Antimicrobial use on 74 Japanese pig farms in 2019: A comparison of Japanese and European defined daily doses in the field

“…Our results also revealed that antimicrobial use monitoring systems at farm level will provide similar results in identification of heavy antimicrobial users regardless of whether the Japanese or European DDD value is used (Fig 3 Our results also revealed that the number of DDDjps/PCU was greater than the number of DDDvets/PCU for all 74 farms analyzed in this study (Fig 3). This was attributed to the fact that DDDjp values are lower than DDDvet values for most antimicrobial agents [19]. Also, this study observed that DDDvets did not cover all the antimicrobial agents used in veterinary medicine in null hypothesis for all datasets being declined, correlation was investigated by Spearman's Rho test and found to be significantly correlated (P<0.001).…”

“…The DDDvet values were available from the EMA website [17]. The detailed procedure for defining the national doses and all DDDjp values are described in a previous report [19]. To calculate the number of DDDvets for those antimicrobial ingredients for which DDDvet is not available, namely sulfamonomethoxine (for injection), tulathromycin (for injection), dihydrostreptomycin (used in combination product for injection), chlortetracycline(used in combination product for injection), sulfamonomethoxine (for oral administration), streptomycin (used in combination product for oral administration), DDDjp value was used instead.…”

“…These values were defined by calculating the mean of dosages of antimicrobial products registered in nine different EU member states. In analogy with the principles of the EMA [18], we have recently assigned national defined daily doses (DDDjp) for antimicrobial agents used in pigs in Japan and verified the need of DDDjp values by comparing them with corresponding DDDvet values [19].…”

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

“…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 ].…”