Consistent rates of kill of Staphylococcus aureus by gentamicin over a 6-fold clinical concentration range in an in vitro pharmacodynamic model (IVPDM).
OBJECTIVE
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 10(6) 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.
Schafer
Jeremy A
JA
Antibiotic Pharmacodynamic Research Institute, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota Minneapolis, MN 55455, USA.
Hovde
Laurie B
LB
Rotschafer
John C
JC
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D005839:Gentamicins / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology
D000900:Anti-Bacterial Agents; D005839:Gentamicins