Pharmacodynamic modeling of colistin and imipenem against

Introduction: Antibiotic treatment of chronic biofilm-associated infections can be challenging. Characterization of pharmacokinetic/pharmacodynamic (PK/PD) relationships for biofilm-associated infections may be relevant to informing the design of antibiotic treatment regimens for biofilm-associated infections. To this end, we aim to develop a mathematical PK/PD model for planktonic and biofilm bacterial infections and demonstrate how PK/PD simulations can be used to design optimized dosing schedules, using colistin and imipenem as proof-of-concept examples. Methods: Pharmacodynamic models were developed using time-kill assay data from planktonic and alginate-bead biofilm cultures of Results: The developed models incorporated susceptible and resistant bacterial subpopulations and were able to adequately capture the observed time-kill data. Simulation studies identified differences in suppression of bacterial growth dynamics for multiple clinical intravenous and inhalation-based treatment regimens and were used to infer biofilm-specific PK/PD indices associated with ELF target site concentrations. Conclusion: In conclusion, we demonstrate the utility of mathematical modeling for the characterization of PK/PD relationships underlying time-kill kinetic profiles in biofilm-associated infections and their utility in translating experimental findings toward clinically relevant dose-optimization strategies.