Activity of linezolid in an in vitro pharmacokinetic-pharmacodynamic model using different dosages and Staphylococcus aureus and Enterococcus faecalis strains with and without a hypermutator phenotype.

ABSTRACT: The influence of antibiotic dosages and bacterial mutator phenotypes on the emergence of linezolid-resistant mutants was evaluated in an in vitro pharmacokinetic-pharmacodynamic model. A twice-daily 0.5-h infusion of a 200-, 600-, or 800-mg dose for 48 h was simulated against four strains (MIC, 2 microg/ml): Staphylococcus aureus RN4220 and its mutator derivative MutS2, Enterococcus faecalis ATCC 29212, and a mutator clinical strain of E. faecalis, Ef1497. The peak concentrations (4.38 to 4.79, 13.4 to 14.6, and 19.2 to 19.5 microg/ml) and half-lives at beta-phase (5.01 to 6.72 h) fit human plasma linezolid pharmacokinetics. Due to its bacteriostatic property, the cumulative percentages of the dosing interval during which the drug concentration exceeded the MIC (T > MIC), 66.6 and 69.1% of

SUBMITTER: Ba BB 

PROVIDER: S-EPMC2849367 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature