Evaluation of co-trimoxazole in the treatment of multidrug-resistant tuberculosis.
SourceEuropean Respiratory Journal, 42, 2, (2013), pp. 504-512
1 augustus 2013
Article / Letter to editor
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European Respiratory Journal
SubjectN4i 3: Poverty-related infectious diseases NCMLS 1: Infection and autoimmunity; N4i 3: Poverty-related infectious diseases NCMLS 1: Infection and autoimmunity
Co-trimoxazole (SXT), a combination of sulfamethoxazole and trimethoprim, has shown in vitro activity against Mycobacterium tuberculosis. However, the pharmacokinetic and pharmacodynamic parameters of SXT in multidrug-resistant (MDR) tuberculosis (TB) are, thus far, lacking. Therefore, we evaluated its pharmacokinetics and drug susceptibility, along with its tolerability during treatment. Based on drug susceptibility testing, MDR-TB patients received SXT as a part of their MDR treatment. The pharmacokinetic parameters of sulfamethoxazole, the effective component of SXT against M. tuberculosis, were evaluated. The ratio of the area under the curve from 0 to 24 h (AUC0-24) to minimum inhibitory concentration (MIC) was used as the best pharmacokinetic/pharmacodynamic parameter to predict the efficacy of sulfamethoxazole. Adverse effects of SXT were also evaluated. 10 patients with MDR-TB (one of whom had extensively drug-resistant TB) received 480 mg of SXT with a median dosage of 6.5 mg.kg(-1) of SXT (range 6.1-6.8 mg.kg(-1)) once daily for a median treatment period of 381 days (range 129-465 days). In two patients, the dose was escalated to 960 mg. The free AUC0-24/MIC of sulfamethoxazole exceeded 25 in only one patient. SXT was safe and well-tolerated, except for one patient who had gastrointestinal side-effects after receiving 960 mg of SXT. Additional studies are needed to find the pharmacokinetic and pharmacodynamic targets, and consequently to set the optimal dose, of SXT for MDR-TB treatment.
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