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 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.