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 (ƒAUC0-24h/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 ƒAUC0-24h/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.