Revisiting co-trimoxazole for the treatment of tuberculosis

Firstly, we systematically reviewed in vitro, in vivo and clinical anti-TB activity of six drugs with antimicrobial activity, which are not listed in WHO guidelines on MDR-TB treatment but could be potential candidates for evaluation against M. tuberculosis. Co-trimoxazole seems most promising.
Secondly, we evaluated PK and drug susceptibility along with the tolerability of sulfamethoxazole against M. tuberculosis in a retrospective study. The ratio of ƒ AUC0-24h/MIC of sulfamethoxazole exceeded 25 in only one patient. Co-trimoxazole was safe and well tolerated; only one patient had side effects.
After that we measured in vitro susceptibility of M. tuberculosis to sulfamethoxazole in drug susceptible TB and co-infected HIV/TB patients and compared these results with the susceptibility of MDR-TB patients in the retrospective study. Because of comparable susceptibility, Co-trimoxazole seems the promising drug for further exploration in the treatment of HIV/TB and MDR-TB patients.
Next we developed a method to measure drug concentration and toxicity in serum and plasma.
Then we performed a prospective study in patients with drug-susceptible TB to optimize PK/PD parameters of sulfamethoxazole in the treatment of TB. These parameters are considered a starting point to explore the efficacy of co-trimoxazole.
Finally, we used dried blood spots (DBS) to determine the concentrations of sulfamethoxazole and its metabolites. This method is suitable for clinical practice, especially in countries with an extremely warm climate.
Future studies are required to show the precise role of sulfamethoxazole in the treatment of TB.