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JAC Advance Access originally published online on May 30, 2006
Journal of Antimicrobial Chemotherapy 2006 58(1):108-111; doi:10.1093/jac/dkl216
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Jeremy A. Schafer, Laurie B. Hovde and John C. Rotschafer*

Antibiotic Pharmacodynamic Research Institute, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota Minneapolis, MN 55455, USA

Received 7 September 2005; returned 25 January 2006; revised 1 February 2006; accepted 8 May 2006

*Correspondence address. Weaver Densford Hall 9-157, University of Minnesota College of Pharmacy, 308 Harvard Street SE, Minneapolis, MN 55455, USA. Tel: +1-612-624-2183; Fax: +1-612-626-5082; E-mail: rotsc001{at}umn.edu

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.

Keywords: single daily dose , adjunctive aminoglycosides , S. aureus , pharmacodynamics


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