Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps.

Abstract

Global rates of pulmonary tuberculosis (TB) continue to increase. Moreover, resistance of the causative organism Mycobacterium tuberculosis to the two most effective anti-TB medications continue to rise. Now, multi-drug resistant TB (MDR-TB) has progressed to extensively drug resistant TB (XDR-TB) - a M. tuberculosis organism that is resistant to the most effective second line drugs available for the treatment of TB. This review provides detailed, significant evidence that supports the use of an old neuroleptic compound, thioridazine (TZ), for the management of MDR-TB and XDR-TB infections and which has been shown to inhibit efflux pumps of bacteria. The argument has been previously presented but no one seems to be listening - and the disease continues unabated when there is a very good probability that the suggested drug will prove to be effective. When the prognosis is poor, available therapy predictably ineffective and death is inevitable, compassionate therapy with TZ should be contemplated. The risks are small and the rewards great.

• Authors: L Amaral, M Martins, M Viveiros, J Molnar, J E Kristiansen
• Journal: Current drug targets (Curr Drug Targets) Vol. 9 Issue 9 Pg. 816-9 (Sep 2008) ISSN: 1873-5592 [Electronic] United Arab Emirates
• PMID: 18781927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antitubercular Agents
• Bacterial Proteins
• Membrane Transport Proteins
• Thioridazine

Topics

• Antitubercular Agents (pharmacology)
• Bacterial Proteins (antagonists & inhibitors, metabolism)
• Drug Resistance, Multiple, Bacterial (drug effects)
• Extensively Drug-Resistant Tuberculosis (drug therapy, epidemiology)
• Humans
• Membrane Transport Proteins (drug effects, metabolism)
• Mycobacterium tuberculosis (drug effects)
• Thioridazine (pharmacology, therapeutic use)
• Tuberculosis, Multidrug-Resistant (drug therapy, epidemiology)