A dynamic in vitro model was used to determine the killing kinetics of daptomycin against 15 vancomycin-resistant clinical isolates of Enterococcus faecium. Concentration profiles simulating those observed in serum following administration of both low-dose (2 mg/kg) and high-dose (6 mg/kg) daptomycin were bactericidal within 5.5 and 2.8 h, respectively. In contrast, when albumin was added to the growth medium, the corresponding bacterial killing times were slowed to greater than 24 h and 7 h; these results suggest that in the clinical setting, daptomycin dosages of approximately 6 mg/kg are required to achieve bactericidal activity against vancomycin-resistant Enterococcus faecium.