The concentration-independent effect of monoexponential and biexponential decay in vancomycin concentrations on the killing of Staphylococcus aureus under aerobic and anaerobic conditions

The Journal of Antimicrobial Chemotherapy
A J LarssonJ C Rotschafer

Abstract

An in-vitro pharmacodynamic system was used to generate time-kill curves to demonstrate the concentration-independent pharmacodynamics of vancomycin against Staphylococcus aureus ATCC 29213. Initial vancomycin concentrations of 5, 10, 20 and 40 mg/L were studied monoexponentially while simulating a 6 h half-life. One parallel experiment was performed in duplicate using an initial peak concentration of 40 mg/L where both a distribution alpha-phase half-life of 0.66 h for 1 h and an elimination beta-phase half-life of 6 h for 11 h were simulated to determine if the transient distribution phase concentrations of vancomycin have any impact on bacterial killing beyond that provided by the elimination phase concentrations. Additionally, two monoexponential experiments with peak concentrations of 40 and 20 mg/L and a half-life of 6 h were repeated in an anaerobic chamber to determine if killing of S. aureus was affected. The time to achieve a 3 log10 kill was calculated from the linear portion of the regression line and averaged (mean +/- S.D.) 9.0 +/- 1.4 h for all aerobic monoexponential experiments and was 8.4 and 8.6 h for the aerobic biexponential experiments (P > 0.05). For the anaerobic studies, the times to reach 3 log10 kill ...Continue Reading

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