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, John C. Rotschafer

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)108-111
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number1
DOIs
StatePublished - Jul 1 2006

Keywords

  • Adjunctive aminoglycosides
  • Pharmacodynamics
  • S. aureus
  • Single daily dose

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