Comparative Pharmacodynamics of Daptomycin and Vancomycin with Staphylococcus aureus in an in vitro Dynamic Model

Abstract

To compare the pharmacodynamics of daptomycin (DAP) and vancomycin (VAN) as well as killing kinetics of S. aureus with different MICs were studied at widely ranged AUC/MIC ratios. Two clinical isolates, S. aureus 866 (MICDAP 0.35 µ/ml and MICVAN 0.70 µ/ml) and S. aureus 10 (MICDAP 1.1 µ/ml and MICVAN 1.3 µ/ml) were exposed to DAP (as a single dose) and VAN (as two 12-h doses). Mono-exponential concentration decay was simulated with half-lives of 9 h (DAP) and 6 h (VAN) and AUC/MIC ratio varied from 43 to 970 h and from 33 to 1150 h respectively. Anti-staphylococcal effects of DAP and VAN depended on the simulated AUC/MICs:the higher the AUC/MIC, the lower numbers of surviving organisms and the later regrowth. Despite pronounced variability of the time-kill curves, AUC/MIC relationships of the ABBC were specific for DAP and VAN. Based on the ABBC-AUC/ MIC relationships, the effects of DAP (4 mg/kg – proposed therapeutic dose) on S. aureus may be greater than those of two 1-g doses of VAN given with a 12-h interval. These findings predict greater anti-staphylococcal effects of clinically achievable AUC/MICs of DAP relative to VAN.