Oritavancin Multiple Dosing for Complex Infections: A Pharmacokinetic/Pharmacodynamic Simulation Study

Background/Objectives: Oritavancin therapy for complex infections remains challenging due to the lack of well-established dosing regimens. The objective of this work was to apply PK/PD modeling and Monte Carlo simulation considering different PK/PD targets to identify multiple dosing regimens that may ensure effective concentrations of oritavancin for the treatment of long-term infections. Methods: Plasma concentration–time profiles were simulated for different regimens (single dose of 1200 mg, 1200 mg followed by 800 mg every 7 days, 1200 mg followed by 800 mg every 10 days, 1200 mg q7d, 1200 mg q10d, 1200 mg every 14 days, 1200 mg every 21 days, and 1200 mg followed by 1200 mg on day 8, then 1200 mg q14d), and the probability of target attainment (PTA), indicative of treatment success, was estimated. Results: All dosing regimens provided probabilities of target attainment of 100% up to MICs of 0.5 mg/L when AUC0-24/MIC and Cmax/MIC were applied. Considering AUC0-72/MIC, the regimens would be adequate up to MIC of 0.125 mg/L. For fCmin > MIC, all except 1200 mg q21d resulted adequate for MIC of 0.125 mg/L, and 1200 mg day 1 + 800 mg q7d, and 1200 mg q10d may be useful to treat infections due to bacteria with MIC of 0.25 mg/L. Conclusions: More studies involving patients with complex infections are needed to better stablish the relationships among plasma concentrations, MIC values, and clinical outcomes. fCmin > MIC should be investigated as a potential PK/PD target for the treatment of these infections with oritavancin.