THE CONCENTRATION-INDEPENDENT EFFECT OF MONOEXPONENTIAL AND BIEXPONENTIAL DECAY IN VANCOMYCIN CONCENTRATIONS ON THE KILLING OF STAPHYLOCOCCUS-AUREUS UNDER AEROBIC AND ANAEROBIC CONDITIONS

An in-vitro pharmacodynamic system was used to generate time-kill curv es to demonstrate the concentration-independent pharmacodynamics of va ncomycin 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 perform ed in duplicate using an initial peak concentration of 40 mg/L where b oth a distribution alpha-phase half-life of 0.66 h for 1 h and an elim ination beta-phase half-life of 6 h for 11 h were simulated to determi ne if the transient distribution phase concentrations of vancomycin ha ve any impact on bacterial killing beyond that provided by the elimina tion phase concentrations. Additionally, two monoexponential experimen ts with peak concentrations of 40 and 20 mg/L and a half-life of 6 h w ere repeated in an anaerobic chamber to determine if killing of S. aur eus was affected. The time to achieve a 3 log(10) 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 wa s 8.4 and 8.6 h for the aerobic biexponential experiments (P > 0.05). For the anaerobic studies, the times to reach 3 log(10) kill were sign ificantly greater averaging 18.9 +/- 1.7 h. The slopes of the bacteria l kill curves were virtually identical for both monoexponential and bi exponential aerobic experiments averaging -0.34 +/- 0.04, yet signific antly different from the anaerobic bacterial kill curve slopes of -0.1 6 +/- 0.015 (P < 0.05). Time-kill curve analyses suggest that varying the concentration of vancomycin does not affect the rate or extent of bacterial killing aerobically or anaerobically against S. aureus and m ore efficient killing was achieved under aerobic conditions. The simul ated distribution phase concentrations did not contribute to more effe ctive killing of this strain of S. aureus.