Pharmacokinetic-pharmacodynamic modeling of dalbavancin, a novel glycopeptide antibiotic

Dalbavancin is a novel glycopeptide with a 2-dose, once--weekly dosing regimen that is being developed for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Monte Carlo simulations were performed for dalbavancin using population pharmacokinetic data and minimum inhibitoiy concentrations (MIGs) for clinical trial isolates. The time-dependent target was the maintenance of free drug concentrations above the MIC for 14 days (t > ABC). The concentration-dependent target was an area under the concentration-time curve (AUG)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcus sp. These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was <= 0.5 mu g/mL using AUC(14 days)/YIMIC and <= mu g/mL using t > MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least 2 yg/mL. Because dalbavancin MIC(90)s for these species are well below these values, the analysis supports the use of once-weekly dosing regimens of dalbavancin in the treatment of complicated skin and skin structure infections.