Efficacy, safety, and population pharmacokinetics of a single 1500mg dose of dalbavancin for short-term therapy in patients with chronic prosthetic joint infections.

Abstract

The efficacy, safety, and population pharmacokinetics of a single 1,500 mg dose of dalbavancin as a sequencing treatment for Gram-positive chronic prosthetic joint infections (CPJIs) have not been described. We present an observational, retrospective study conducted in two Spanish hospitals including patients with CPJI caused by Gram-positive bacteria susceptible to dalbavancin managed with two-stage exchange, antibiotic-loaded spacers, and a single 1,500 mg dose of dalbavancin. Follow-up visits included measurement of dalbavancin plasma concentrations. Negative intraoperative cultures at second-stage surgery defined microbiological cure. Population pharmacokinetics and Monte Carlo dosing simulations were used to evaluate whether this dose provided a therapeutic antibiotic exposure defined as the ratio between the area under the unbound concentration curve and the bacteria minimum inhibitory concentration (ƒAUC_0-24h/MIC) ≥ 50 for the entire treatment period. Twenty patients were included, with CPJI mostly caused by coagulase-negative staphylococci (71%). After 11.5 days of intravenous antibiotic therapy (vancomycin, 75%), patients received 1,500 mg of dalbavancin without adverse events. Microbiological cure was 94.7% (median follow-up, 693 days). Dosing simulations suggest that a single 1,500 mg dose of dalbavancin is sufficient for maintaining ƒAUC_0-24h/MIC ≥ 50 for MIC ≤ 0.25 mg/L for 3-4 weeks after administration. A single 1,500 mg dose of dalbavancin combined with antibiotic-loaded spacers may be an effective and safe sequencing treatment for CPJI and provide 3-4 weeks of therapeutic exposure for susceptible microorganisms. Considering dalbavancin's unique pharmacokinetics, this approach may be considered in the clinical management of CPJI.