Pharmacokinetic and pharmacodynamic concepts in antibiotic therapy for clinicians

Abstract

Antibiotic efficacy depends on attaining adequate drug exposure at the site of infection while minimizing toxicity and resistance selection. This clinician-oriented review integrates pharmacokinetic determinants of exposure with pharmacodynamic drivers of bacterial killing. Emphasis is placed on the relevance of unbound concentrations, tissue distribution, and the limitations of MIC-based targets when interpreted without appropriate biological and microbiological context. Determinants of antibiotic performance are examined from an integrated perspective, considering drug-related properties, microorganism characteristics, host factors, and features intrinsic to the infectious process. Practical implications for regimen design are addressed, including loading doses, dose intensity, and infusion strategies aimed at optimizing exposure profiles. Mechanisms connecting suboptimal exposure with resistance amplification are discussed, with particular attention to selective pressure and the mutant selection window. Therapeutic drug monitoring and model-informed dose adjustment are presented as complementary tools to support more precise and rational antibiotic dosing.