title: Trimethoprim-sulfamethoxazole activity and pharmacodynamics against glycopeptide-intermediate Staphylococcus aureus.
abstract: 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.
authors.affiliation: Infectious Disease Research Laboratory, College of Pharmacy, University of Toledo, Ohio 43606, USA.
authors.forename: Sandy J
authors.initials: SJ
authors.lastname: Close
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McBurney
authors.forename: Cory G
authors.initials: CG
authors.lastname: Garvin
authors.forename: David C
authors.initials: DC
authors.lastname: Chen
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Martin
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D015662:Trimethoprim, Sulfamethoxazole Drug Combination