OBJECTIVES: 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.
OBJECTIVES: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: Andi Rofian Sultan; Mehri Tavakol; Nicole A Lemmens-den Toom; Peter D Croughs; Nelianne J Verkaik; Annelies Verbon; Willem J B van Wamel Journal: PLoS One Date: 2022-02-16 Impact factor: 3.240
Authors: Fabrício Rodrigues Torres de Carvalho; João Paulo Telles; Felipe Francisco Bodan Tuon; Roberto Rabello Filho; Pedro Caruso; Thiago Domingos Correa Journal: Antibiotics (Basel) Date: 2022-03-12