Post-antibiotic and post-antibiotic sub-MIC effects of gentamicin, sophoraflavanone G, and their combination against a clinical isolate of Staphylococcus aureus

Abstract

Abstract Background: Post-antibiotic effect (PAE) defines the potential of a drug to delay re-growth of a bacterial population after short-term exposure and removal of a drug. Determination of the PAE is recommended in preclinical evaluation of all new antimicrobial agents, because it influences optimal antimicrobial dosing intervals. Objective: Evaluate the PAE and PA-SME of gentamicin and sophoraflavanone G against Staphylococcus aureus (S. aureus) itself and in combination. Methods: A spectrophotometric method was used to determine the PAE and PA-SME. Results: Sophoraflavanone G and gentamicin, showed considerable PAE and PA-SME at the tested concentrations against S. aureus. The increased duration of PAE caused by sophoraflavanone G and gentamicin was dosedependent. In addition, sophoraflavanone G at sub-MIC concentrations enhanced the PAE and PA-SME of gentamicin in a dose-dependent manner. The highest enhancing effect was observed for gentamicin at the synergistic MIC and 1/2 the synergistic MIC levels against S. aureus 0.03 μg/mL (30 ng/mL) of sophoraflavanone G (with PAE=55 minutes). It enhanced the post-antibiotic sub-MIC effect (PA-SME) duration of gentamicin at concentrations of 4 μg/mL from 15 minutes to 80 minutes (a six-fold increase). Conclusion: Sophoraflavanone G is promising for the preparation of an effective therapeutic formulation against gentamicin-resistant S. aureus.