Effect of human serum on the bactericidal activity of daptomycin and vancomycin against staphylococcal and enterococcal isolates as determined by time-kill kinetic studies

The bactericidal activity of daptomycin and vancomycin alone in cation-supplemented Mueller-Hinton broth and in human serum against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis was evaluated by exposing replicating microorganisms to concentrations ranging from 2 to 128 μg/ml for 24 hr. In addition, the possibility of emergence of resistance, the stability of each agent in the respective medium, and the percent of protein binding by human serum for each agent was evaluated. We found that a concentration of ⩽ 8 μg/ml of daptomycin was sufficient to achieve bactericidal activity (⩾99.9% killing of the inoculum) in cation-supplemented Mueller-Hinton broth for all staphylococcal isolates tested; a concentration of ⩽ 16 μg/ml of daptomycin was required for bactericidal activity in cation-supplemented Mueller-Hinton broth for enterococcal isolates. In human serum, comparable bactericidal activity with daptomycin was achieved only with concentrations 8–16 times higher. A similar but less pronounced effect in human serum was seen for vancomycin. Neither daptomycin nor vancomycin was appreciably degraded in human serum over a 24-hr period. It is likely that the clinical efficacy of daptomycin in humans would be enhanced by higher dosing than has been studied to date.