International Journal of Antimicrobial Agents
Volume 35, Issue 6 , Pages 524-526 , June 2010

Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!

  • Leonard Amaral

      Affiliations

    • Unit of Mycobacteriology/UPMM, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    • Corresponding Author InformationCorresponding author.
    • ,
  • Martin J. Boeree

      Affiliations

    • Radboud University Nijmegen Medical Centre and ULC Dekkerswald, Nijmegen, The Netherlands
    • ,
  • Stephen H. Gillespie

      Affiliations

    • University College London, Centre for Medical Microbiology, Royal Free Campus, Rowland Hill Street, London, UK
    • ,
  • Zarir F. Udwadia

      Affiliations

    • Hinduja Hospital and Research Center, Mumbai, India
    • ,
  • Dick van Soolingen

      Affiliations

    • Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

References 

  1. Faustini A, Hall AJ, Perucci CA. Risk factors for multidrug resistant tuberculosis in Europe: a systematic review. Thorax. 2006;61:158–163
  2. Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, Cauthen GM, Dooley SW. The emergence of drug-resistant tuberculosis in New York City. N Engl J Med. 1993;328:521–526
  3. Munsiff SS, Bassoff T, Nivin B, Li J, Sharma A, Bifani P, et al. Molecular epidemiology of multidrug-resistant tuberculosis, New York City, 1995–1997. Emerg Infect Dis. 2002;8:1230–1238
  4. World Health Organization. Anti-tuberculosis drug resistance in the world. Report No. 4. Geneva, Switzerland: WHO; 2008.
  5. Perdigão J, Macedo R, João I, Fernandes E, Brum L, Portugal I. Multidrug-resistant tuberculosis in Lisbon, Portugal: a molecular epidemiological perspective. Microb Drug Resist. 2008;14:133–143
  6. Velayati AA, Masjedi MR, Farnia P, Tabarsi P, Ghanavei J, Ziazarifi AH, et al. Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran. Chest. 2009;136:420–425
  7. Amaral L, Kristiansen JE, Abebe LS, Millet W. Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for the initial therapy of freshly diagnosed tuberculosis. J Antimicrob Chemother. 1996;38:1049–1053
  8. Ordway D, Viveiros M, Leandro C, Amaral L. Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2003;47:917–922
  9. Martins M, Viveiros M, Amaral L, Couto I, Molnar J, Boeree M, et al. SILA 421, an inhibitor of efflux pumps of cancer cells, enhances the killing of intracellular extensively drug-resistant tuberculosis (XDR-TB). Int J Antimicrob Agents. 2008;33:479–482
  10. Martins M, Viveiros M. Amaral l. The curative activity of thioridazine on mice infected with Mycobacterium tuberculosis. In Vivo. 2007;21:771–776
  11. Abbate E, Vescoso M, Natiello M, Cufre M, Garcia A, Ambroggi M, et al. Tuberculosis extensamente resistente (XDR-TB) en Argentina: aspectos destacbles epidemiologicos, bacteriologicos, terapeuticos y evolutivos. Revista Argentina de Medicina Respiratoria. 2007;1:19–25
  12. Thanacoody HKR. Thioridazine: resurrection as an antimicrobial agent?. Br J Clin Pharmacol. 2007;64:566–574
  13. Udwadia ZF. India's multidrug-resistant tuberculosis crisis. Ann N Y Acad Sci. 2001;953:98–105
  14. Mitnick CD, Castro KG, Harrington M, Sacks LV, Burman W. Randomized trials to optimize treatment of multidrug-resistant tuberculosis. PLoS Med. 2007;4:e292
  15. Mitchison DA. Clinical development of anti-tuberculosis drugs. J Antimicrob Chemother. 2006;58:494–495

PII: S0924-8579(10)00021-X

doi: 10.1016/j.ijantimicag.2009.12.019

International Journal of Antimicrobial Agents
Volume 35, Issue 6 , Pages 524-526 , June 2010

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