Pharmacodynamics of dalbavancin studied in an in vitro pharmacokinetic system

Objectives: The antibacterial effect of dalbavancin was studied against Staphylococcus aureus using stepwise declining concentrations designed to model a range of free drug concentrations observed in human serum. Methods: Initial concentrations ranged from 0.6 to 21 mg/L and experiments were conducted over 240 h. Three vancomycin-susceptible and one vancomycin-intermediate strain of S. aureus were used. Results and conclusions: Dalbavancin showed non-concentration-dependent killing against the three vancomycin-susceptible strains in the range 3-21 mg/L and the vancomycin-intermediate strain at 15 and 21 mg/L. AUC/MIC could be related to antibacterial effect. The AUC/MIC for a bacteriostatic effect was 36 at 24 h, 55 at 120 h and 100 at 240 h. A larger AUC/MIC was required to produce a 2 log reduction in counts, being 214 at 24 h, 195 at 120 h and 331 at 240 h.