Defining the Active Fraction of Daptomycin against Methicillin-Resistant Staphylococcus aureus (MRSA) Using a Pharmacokinetic and Pharmacodynamic Approach.

ABSTRACT: Our objective was to study the pharmacodynamics of daptomycin in the presence of varying concentrations of human serum (HS) in vitro to quantify the fraction of daptomycin that is 'active'. Time kill experiments were performed with daptomycin (0 to 256 mg/L) against two MRSA strains at log-phase growth, in the presence of HS (0%, 10%, 30%, 50%, 70%) combined with Mueller-Hinton broth. Daptomycin ≥ 2 mg/L achieved 99.9% kill within 8 h at all HS concentrations; early killing activity was slightly attenuated at higher HS concentrations. After 1 h, bacterial reduction of USA300 upon exposure to daptomycin 4 mg/L ranged from -3.1 to -0.5 log10CFU/mL in the presence of 0% to 70% HS, respectively. Bactericidal activity was achieved against both strains at daptomycin ≥ 4 mg/L for all fractions of

SUBMITTER: Garonzik SM 

PROVIDER: S-EPMC4902307 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature