Trimethoprim-sulfamethoxazole activity and pharmacodynamics against glycopeptide-intermediate Staphylococcus aureus

Study Objective. To determine the activity of trimethoprim-sulfamethoxazole (TMP-SMX) against glycopeptide-intermediate Staphylococcus aw-cits (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 I x MIC and at simulated peal, serum concentrations (C-max), 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 C-max. 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.