Trimethoprim-sulfamethoxazole activity and pharmacodynamics against glycopeptide-intermediate Staphylococcus aureus.
OBJECTIVE
To determine the activity of trimethoprim-sulfamethoxazole (TMP-SMX) against glycopeptide-intermediate Staphylococcus aureus (GISA).


METHODS
In vitro study.


METHODS
University laboratory.


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.


CONCLUSIONS
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.
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Sandy J
SJ
Infectious Disease Research Laboratory, College of Pharmacy, University of Toledo, Ohio 43606, USA.
McBurney
Christopher R
CR
Garvin
Cory G
CG
Chen
David C
DC
Martin
Steven J
SJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D006020:Glycopeptides; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D015662:Trimethoprim, Sulfamethoxazole Drug Combination