Chemotherapeutic efficacy of thioridazine as an adjunct drug in a murine model of latent tuberculosis

Thioridazine, a potent phenothiazine compound was evaluated for its chemotherapeutic efficacy against experiment model of tuberculosis. Thioridazine potentiated the activities of both isoniazid and rifampicin (>1 log CFU reduction) against the in vitro latent Mycobacterium tuberculosis bacilli. Further, a murine model of latent tuberculosis was used and the standard 9-month isoniazid and 4-month rifampicin regimen along with thioridazine as an adjunct drug were evaluated. Thioridazine led to an accelerated clearance of bacilli with both the regimen, thereby leading to completion of therapy much earlier than the standard end-point. In the case of 9-month isoniazid regimen, when thioridazine was used along with isoniazid as an adjunct drug, complete clearance was observed as early as 24 weeks as compared to the 36 week standard isoniazid monotherapy regimen. Also, in the 4-month rifampicin regimen, it was observed that the bacillary clearance was more robust when rifampicin was used along with thioridazine (>3 log CFU reduction) than rifampicin alone (>2 log CFU reduction). Our findings implicate that thioridazine, when used as an adjunct drug along with isoniazid or rifampicin has the potential to augment their chemotherapeutic efficacy against experimental latency.