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 inhibitory concentrations (MICs) for clinical trial isolates. The time‐dependent target was the maintenance of free drug concentrations above the MIC for 14 days (t > MIC). The concentration‐dependent target was an area under the concentration‐time curve (AUC)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcussp. These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was ≤0.5 μg/mL using AUC14 days/MIC and ≤1 μg/mL using t > MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least 2 μg/mL. Because dalbavancin MIC90s 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.