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Trimethoprim-sulfamethoxazole activity and pharmacodynamics against glycopeptide-intermediate Staphylococcus aureus
Sandy J Close1, Christopher R McBurney, Cory G Garvin
1Infectious Disease Research Laboratory, College of Pharmacy, University of Toledo, Ohio 43606, USA.
Study Objective:
To determine the activity of trimethoprim-sulfamethoxazole (TMP-SMX) against glycopeptide-intermediate Staphylococcus aureus (GISA).
Design:
In vitro study.
Setting:
University laboratory.
Measurements And Main Results:
Minimum inhibitory concentrations (MICs) of TMP-SMX were determined for three GISA strains. Time-kill assays were conducted at 1 x MIC and at simulated peak serum concentrations (Cmax). Two dosing regimens of TMP-SMX were investigated: TMP-SMX 8 mg (TMP)/kg/day and TMP-SMX 15 mg/kg/day, each divided into two doses/day Both dosages were studied against each strain in a two-compartment in vitro model to determine concentration-related activity. All isolates were susceptible to TMP-SMX. In time-kill studies at 1 x MIC, TMP-SMX was bacteriostatic against all isolates and bactericidal against two of three strains at simulated Cmax. The 15 mg/kg/day (divided-dose) regimen provided the best overall reduction in colony-forming units/ml.
Conclusion:
All GISA strains were susceptible to TMP-SMX. In addition, it appears that TMP-SMX may have concentration-dependent antibacterial activity against these organisms. As an option in the management of GISA infection, TMP-SMX merits further study.