A cost–benefit analysis of the application of pharmacokinetic/pharmacodynamic-based approaches to setting disc diffusion breakpoints in aquaculture: A case study of oxolinic acid and Aeromonas salmonicida

The last decade has seen a dramatic revolution in approaches to setting breakpoints for antimicrobial susceptibility data with respect to human pathogens. These involve extensive application of pharmacokinetic (PK) and pharmacodynamic (PD) data and the processing of these data with statistical tools, such as Monte Carlo simulation. This review attempts a cost–benefit analysis of the application of these approaches to the setting of disc diffusion breakpoints for bacteria associated with diseases of fish. It is argued that, with respect to metaphylactic treatments of fish, a number of factors present major problems for the collection of requisite PK and PD data. These include the wide diversity of the environmental contexts in which antimicrobial therapies are applied to a diverse range of fish species and the difficulties encountered in multiple sampling of individual fish. An analysis of the data we require, and the data we already possess, suggests that, even if the theoretical and practical problems can be overcome, the application of the PK/PD approach would require significant investment of time, money and expertise. An analysis is also presented of the potential benefits that might be expected from the application of PK/PD analysis to the setting of breakpoints relevant to fish therapies. This analysis was performed on data relevant to the treatment of infections by Aeromonas salmonicida with orally administered oxolinic acid and it indicated that the benefits that might accrue would be marginal.The overall conclusion presented here is that the investment required to develop the requisite PK/PD data in fish cannot be justified by improvements that might result in the advice that laboratories can offer fish health care professionals.