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Latent tuberculosis: is there a role for thioridazine?

Abstract
Approximately 1/3 of the world's population is infected with Mycobacterium tuberculosis. In the vast majority of cases this results in latent not active disease. Latent disease is defined as a positive reaction to tuberculin antigens but without any further clinical symptoms. Models have been developed to study latent tuberculosis with the two most prominent being the in vivo murine model and the in vitro Wayne model. In both cases M. tuberculosis undergoes a change in its respiratory profile as it shifts down to a nonreplicating state. However in both the mouse and the Wayne model, dormant M. tuberculosis is sensitive to the phenothiazine thioridazine. This antibiotic has several targets, and the main one is respiration. There is a growing burden of multidrug resistant and extensively drug resistant tuberculosis. Treatment of these cases is expensive with high mortality. We propose that thioridazine alone, or with other antibiotics, be used to treat drug resistant latent tuberculosis. The advantages are that thioridazine is inexpensive, effective against drug resistant tuberculosis, well characterized and unlikely to induce drug resistance. The disadvantages include possible side effects, although these should be rare at the doses and length of time of treatment. Recent patents involving analogs of thioridazine suggest this class of drugs may hold great promise for the future treatment of the most drug resistant strains.
AuthorsCharles Sohaskey
JournalRecent patents on anti-infective drug discovery (Recent Pat Antiinfect Drug Discov) Vol. 6 Issue 2 Pg. 139-46 (May 2011) ISSN: 2212-4071 [Electronic] Netherlands
PMID21548878 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Review)
Chemical References
  • Antitubercular Agents
  • Thioridazine
Topics
  • Animals
  • Antitubercular Agents (adverse effects, therapeutic use)
  • Drug Discovery
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Humans
  • Latent Tuberculosis (drug therapy, microbiology)
  • Mycobacterium tuberculosis (drug effects, pathogenicity)
  • Patents as Topic
  • Thioridazine (adverse effects, therapeutic use)
  • Treatment Outcome

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