Totally Drug Resistant Tuberculosis can be treated with thioridazine in combination with antibiotics to which the patient was initially resistant.

Abstract

infection is presented. Thioridazine is an old neuroleptic that replaced the first commercial neuroleptic chlorpromazine (trade name lactargil) inasmuch as the former produced fewer serious side effects than the latter. Thioridazine however, is not free of serious side effects. Albeit infrequently, it may produce prolongation of QT interval (time between heart beats), arrhythmia, tordade de pointes, and rarely, even sudden death [2]. However, with proper attention to these potential problems, cardiac monitoring prior to and during initial therapy with thioridazine is commenced at a low dose that is increased slowly, the drug is relatively safe when compared to other newer and more commonly used neuroleptics [2]. The in vitro antitubercular properties of thioridazine were first described more than 15 years ago [3] at the time that resurgence of tuberculosis and its multi-drug resistant forms of infection were noted world-wide. However, the concentrations needed to completely inhibit the in vitro replication of the organism were clinically irrelevant given that these concentrations were in the range of 25 to 30 mg/L and the maximum safe level that can be achieved in the patient is ca. 0.5 mg/L of plasma. Crowle et al. [4] had demonstrated that chlorpromazine enhanced the killing of intracellular Mycobacterium tuberculosis at a concentration in the medium that was in the range present in plasma of a chronically treated with this neuroleptic. Given that tuberculosis is essentially an intracellular infection, the question of whether thioridazine, the equal to chlorpromazine as an in vitro tubercular agent [3], has similar intracellular activity against multi-drug resistant Mycobacterium tuberculosis, was soon investigated and shown to promote the killing of intracellular multi-drug resistant Mycobacterium tuberculosis by non-killing human macrophages at a concentration that was close to that initially used to treat a freshly diagnosed case of pyschosis [5]. Thioridazine has been shown to cure the mouse of an antibiotic susceptible [6] and multi-drug resistant [7] infections and most recently, shown to cure patients infected with extensively drug resistant strains of Mycobacterium tuberculosis when used in combination with antibiotics to which the patients were initially resistant [8]. When used as monotherapy, thioridazine has been +