Comparative in vitro activity of daptomycin (LY146032) and vancomycin against gram-positive cocci determined using a pharmacokinetic model

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Abstract
The activity of daptomycin (LY146032) and vancomycin was compared for methicillin-sensitive and methicillin-resistant (MRSA) strains ofStaphylococcus aureus and forEnterococcus faecalis, using a semi-automated model that allows examination of time-kill curves with diminishing drug concentrations, thus reflecting in vivo pharmacokinetics. Exposure to daptomycin resulted in rapid killing of all strains of staphylococci andEnterococcus faecalis tested. Methicillin-sensitive staphylococcal strains appeared marginally more susceptible than MRSA. By contrast, the activity of vancomycin appeared much reduced. For all strains, >90% kill was not observed within 24 h.Enterococcus faecalis was uniformly less susceptible to both agents than were staphylococci. The results suggest that despite similar values for MICs, the activity of daptomycin against strains ofStaphylococcus aureus andEnterococcus faecalis is comparable to and may exceed that of vancomycin, although the significance of such differences is uncertain.