Antibiotic treatment for animals: effect on bacterial population and dosage regimen optimisation.

Concern regarding antimicrobial resistance has led to proposals for the prudent use of antimicrobial agents. Whilst this is appropriate, it is not sufficient. This article proposes that dosage schedules should be developed to provide a basis for the rational use of antimicrobial drugs. This requires knowledge of resistance mechanisms and transfer, the biochemistry and structure of microorganisms and both the pharmacodynamics and pharmacokinetics of antimicrobial drugs. Dosage schedules should maintain concentrations at the site of infection in excess of MIC(90) for bacteriostatic drugs and bactericidal drugs acting primarily by time-dependent mechanisms whilst they should provide high AUIC and C(max)/minimum inhibitory concentration (MIC) values for agents acting mainly by concentration-dependent mechanisms. It is proposed that pharmacodynamic and population pharmacokinetic data should be integrated through use of the sigmoidal E(max) equation, together with mathematical modelling and appropriate statistical analyses, to take account of the natural variation in drug pharmacodynamics and pharmacokinetics.