A General Analytic Approach to Predicting the Best Antibiotic Dosing Regimen

Abstract

Determining optimal antibiotic dosing strategies is complex. Clinically, some antibiotics work best in continuous low doses, while others require high repeated pulses. However, a rational understanding of the best approach depending on the specific pairing of antibiotic and bacterial species remains unclear. Using mathematical models, we analyze bacterial populations under two strategies - constant concentration and repeated dosing - given fixed pharmacodynamic and pharmacokinetic properties. Our results reveal that the shape of the dose-response curve, which measures bacterial net growth rate against antibiotic concentration, is crucial. Specifically, its concavity determines the best strategy. In cases where the curve exhibits multiple concavities, additional factors such as tolerable dosing range influence the regimen. These findings challenge the universal application of "hit hard and hit early," as some recommended schedules include lower, constant doses. This work contributes to the literature on rational antibiotic prescription, aiming to minimize antibiotic use and combat antimicrobial resistance.