Daptomycin tailored dosing: a pharmacometric approach

To deal with multi-drug resistant bacteria, research in infectiology has provided different solutions, from the development of a last-resort antibiotic such daptomycin to the fine optimization of antibiotic dosing regimens. As introduction to the present assay, a state-of-the-art review about daptomycin pharmacological properties and clinical applications is given, together with basic explanations about PK/PD models, population pharmacokinetics (POP/PK) models and Monte Carlo Simulation-based pharmacokinetics prediction systems. The aim of the present work is to improve the daptomycin POP/PK model initially developed by Di Paolo and colleagues basing on data collected from patients affected by severe Gram-positive infections. More than 30 new patients have been added to the original database, according to the inclusion criteria stated in the AOUP's #55945 DAPTOLIN retrospective observational research protocol. Plasma daptomycin concentrations are assessed with an HPLC method in the context of routine AOUP TDM clinical workflow. Model building and validation is performed using NONMEM 7.2 (ICON plc) for the structural and statistical components, and with R's plugin Xpose4 for the covariate component and for graphic evaluations