Integrative model-based comparison of target site-specific antimicrobial effects: A case study with ceftaroline and lefamulin

Predictions of antimicrobial effects typically rely on plasma-based pharmacokinetic-pharmacodynamic (PK-PD) targets, ignoring target-site concentrations and potential differences in tissue penetration between antibiotics. In this study, we applied PK-PD modelling to compare target site-specific effects of antibiotics by integrating clinical microdialysis data, in vitro time-kill curves, and antimicrobial susceptibility distributions. As a case study, we compared the effect of lefamulin and ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) at soft-tissue concentrations.