Evaluation of Co-trimoxazole in treatment of multidrug-resistant tuberculosis

Co-trimoxazole (SXT), a combination of sulfamethoxazole (SMX) and trimethoprim has shown in vitro activity against Mycobacterium tuberculosis. However, the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of SXT in multidrug-resistant (MDR) tuberculosis (TB) are so far lacking. Therefore we evaluated the PK 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 PK parameters of SMX, the effective component of SXT against Mycobacterium tuberculosis were evaluated. The ratio of AUC0-24h/MIC was used as the best PK/PD parameter to predict the efficacy of SMX. Adverse effects of SXT were also evaluated. Ten patients with MDR-TB (one of whom had XDR-TB) received 480 mg of SXT with median dose of 6.5 mg/kg of SXT (Range, 6.1-6.8) qd for a median treatment period of 381 days (Range, 129-465). In two patients, the dose was escalated to 960 mg. ƒAUC0-24/MIC of SMX 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 PK/PD targets and consequently to set the optimal dose of SXT for MDR-TB treatment.