Consistent rates of kill of Staphylococcus aureus by gentamicin over a 6-fold clinical concentration range in an in vitro pharmacodynamic model (IVPDM)

Objectives: To compare the effect of a 6-fold range in gentamicin concentration on the bacterial killing of Staphylococcus aureus. Methods: Six 24 h duplicate experiments were performed using an in vitro pharmacodynamic model (IVPDM) which was inoculated with 106 cfu/mL S. aureus (ATCC 29213) and subjected to desired initial gentamicin concentrations of 0, 5, 10, 15 and 20 mg/L. A 2 h half-life was emulated for gentamicin. Samples were drawn at 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 24 h to quantify cfu/mL and gentamicin concentration. These samples were subjected to serial saline dilution to prevent antibiotic carryover and to produce a countable number of colonies. Pre- and post-gentamicin MIC values were performed for S. aureus. Duplicate 24 h kill curves were generated for each experiment and assessed for statistical difference (two-way ANOVA) between the slopes of the kill curves and time to 3 log kill. Results: Kill curve slopes were analysed out to the 2 h time point and no statistical difference was found between the different concentrations (P > 0.05). Time to 3 log kill was not significantly different between the concentrations. Post-exposure gentamicin MIC values were within one tube dilution of the pre-exposure MIC value (0.25 mg/L). Conclusions: These data demonstrate that clinical gentamicin concentrations kill S. aureus with equivalent effectiveness and that the use of higher doses of aminoglycosides would probably not improve bacterial kill rates.