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Updated: May 7, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Serum concentration of co-trimoxazole during a high-dosage regimen
Sirwan Muhammed Ameen1, Jean-Marc Rolain, Marie-Noelle Le Poullain
1Aix-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.
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.
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