title: Serum concentration of co-trimoxazole during a high-dosage regimen.
abstract: OBJECTIVE
  Sulfamethoxazole and trimethoprim have been used for decades, yet high dosages are rarely reported. We aimed to measure blood concentrations of both molecules in this situation.
  
  
  METHODS
  Between 2002 and 2010, 22 patients received two tablets of co-trimoxazole three times a day, equivalent to a daily dosage of 2400 mg of sulfamethoxazole and 480 mg of trimethoprim. The trimethoprim and sulfamethoxazole concentrations were determined 3 h after administration using ion-paired HPLC.
  
  
  RESULTS
  In the presence of a negative control, which yielded no peaks at the retention times for trimethoprim and sulfamethoxazole, the mean ± SD value for sulfamethoxazole concentration was 161.01 ± 69.154 mg/L and the mean ± SD value for trimethoprim was 5.788 ± 2.74 mg/L.
  
  
  CONCLUSIONS
  These concentrations are largely above the trimethoprim and sulfamethoxazole MIC distributions as well as the trimethoprim resistance clinical breakpoint (4 mg/L) reported by EUCAST in 2012 for most bacterial pathogens, including Gram-positive species such as Staphylococcus aureus. Our results support proposing a high-dosage regimen of co-trimoxazole as a suitable alternative for methicillin-resistant S. aureus infections.
authors.affiliation: Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UMR CNRS 7278, IRD 198, INSERM 1095, Faculté de Médecine, Marseille, France.
authors.forename: Sirwan
authors.initials: S
authors.lastname: Muhammed Ameen
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Rolain
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Le Poullain
authors.forename: Véronique
authors.initials: V
authors.lastname: Roux
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.forename: Michel
authors.initials: M
authors.lastname: Drancourt
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D044967:Serum / Q000737:chemistry*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
keywords: MRSA; sulfamethoxazole; trimethoprim