Clinical Microbiology and Antimicrobial Chemotherapy. 2006; 8(2):186-192
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.