Thioridazine as an Adjunct for Therapy of Multi-Drug (MDR), Extensively Drug Resistant (XDR) and Totally Drug Resistant (TDR) Pulmonary Tuberculosis Infections

Abstract

Pulmonary tuberculosis (TB), once thought to be on track for complete elimination during the 1950’s as a consequence of improved social conditions, delivery of public health, diagnosis and therapy with the two most effective anti-tubercular agents Isoniazid (INH) and Rifampicin (Rif), has, as a consequence of social and political strife which reduced or reversed the positive trends of the 1950’s, returned with a vengeance. And because of the large migrations of peoples from where the resurgence of pulmonary tuberculosis took place, the countries and cities that received these migrants also have experienced a huge resurgence of TB [1]. However, although therapy of pulmonary TB is almost always successful with INH and Rif, poor delivery of therapy has resulted in the selection of mutants that spontaneously arise from the prolonged period of therapy, and these are immune to the effectiveness of INH and Rif. This resistance is termed MDR TB and although the recent World Health Organisation Report suggests that the increased frequency of global MDR TB has for the first time plateaued [2], the fact that faithful and accurate reporting by countries such as India which has the largest population of pulmonary TB and MDR TB in the world, is suspect, and in all probability, MDR TB continues to increase globally [3]. And because MDR TB under the best circumstances is problematic for therapy, the increase of global MDR, in effect, is expected to continue. The problem with MDR TB infections has now progressed to a further level of resistance which is termed extensive drug resistance (XDR). XDR TB is resistant to INH, Rif, to any quinolones, streptomycin, and any of the intravenous anti-TB drugs amikacin, capreomycin and kanamycin. If this highly pulmonary TB infection is worrisome, there is now increasing evidence that the