Selecting Antimicrobial Drugs and Dosing Schedule Optimisation Using PK/PD Characteristics

Although successful therapy is the primary purpose of the antimicrobial treatment of diseased animals, the food safety of products made from animals once they are healthy and animals’ production statuses are also vital. Veterinarians, in their practices, therefore must make decisions while considering and weighing the merits of several medical views: assessments of clinical signs, bacteriological investigation, the expected efficacy of the selected drug, the animals’ welfare, risks of resistance development and a consideration of residues and their depletion (altogether influencing also the cost-effectiveness of treatment, i.e. a nonmedical view). For antimicrobial therapy to be considered effective, it must deliver clinical cure (but not necessarily in all cases achieving also bacteriological cure), and for this, selecting the optimal antimicrobial, taking the appropriate route of administration and using the best possible dosing schedule are vital. The three principal factors of this schedule are dose, frequency and duration. To determine the best therapy according to the above requirements, this chapter provides an overview of the interactions among antimicrobials and disease-causing microorganisms, including the potency and efficacy of antimicrobials, and the mechanisms of inhibiting/killing the pathogen, in the case of the susceptibility to concentrations achievable in the target tissue. Attention is also paid to pharmacological and toxicological effects and emerging resistances (pharmacodynamic perspective). To take the most comprehensive picture possible, characteristics important for the antimicrobial administration, together with the antimicrobial’s action and behaviour inside the bodies of diseased animals (pharmacokinetic perspective) and the key variables related to the drug, its medicinal properties, its route of administration, the dose and interlinked absorption, distribution, metabolism and excretion (ADME) parameters, ensuring the achievement of an effective concentration at the site of infection for a sufficient period of time are described. The essential facts of the pharmacodynamic (PD) and pharmacokinetic (PK) indices and their uses are briefly summarised, including comments on the use of PK/PD models working with robust results reached via well-designed clinical trials and can help to set up dosing schedules for the effective therapy, once modelled data is verified by clinical studies.