Antibiotic dosing is routinely evaluated through drug exposure, bacterial suppression, and clinical response, whereas evolutionary consequences may emerge across different populations and timescales. A regimen can reduce the susceptible pathogen burden while enriching resistant survivors, altering commensal competition, or leaving ecological opportunities that persist after drug clearance. This original pharmacological theory proposes that antibiotic outcomes arise from the relative timing of five partially coupled processes: active exposure at microbial niches, bactericidal or growth-suppressive response, phenotypic survival and memory, heritable resistance selection, and community reassembly. Evidence from antimicrobial pharmacokinetics, experimental evolution, bacterial physiology, and gut-microbiome studies supports the relevance of these processes individually, but does not validate their proposed integration as a universal dosing rule. The theory differentiates absolute killing from changes in resistance frequency and distinguishes microbiome structural return from functional or resistome recovery. It predicts that regimens with similar summary pharmacokinetic–pharmacodynamic indices may produce different evolutionary outcomes when tissue exposure, survivor-state duration, population bottlenecks, or recovery conditions differ. Longitudinal, compartment-resolved experiments are needed before these predictions can guide clinical dosing.
IJPRAS
