Advanced search
Publication Cover
Expert Review of Anti-infective Therapy Volume 10, 2012 - Issue 8
Submit an article Journal homepage
82
Views
5
CrossRef citations to date
0
Altmetric
Perspective

Why and how thioridazine in combination with antibiotics to which the infective strain is resistant will cure totally drug-resistant tuberculosis

Leonard Amaral Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1349-008 Lisbon, Portugal. [email protected]; Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1349-008 Lisbon, Portugal. [email protected]
&
Joseph Molnar Institute of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary; Institute of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary
Pages 869-873 | Published online: 10 Jan 2014

References

  • WHO/IUATLD. Global Project on Anti-tuberculosis Drug Resistance Surveillance. Fourth Global report. WHO, Geneva, Switzerland (2008).
  • Centers for Disease Control and Prevention (CDC). Plan to combat extensively drug-resistant tuberculosis: recommendations of the federal tuberculosis task force. Morb. Mortal. WklyRep. 58(RR-3), 1–43 (2009).
  • Udwadia ZF, Amale RA, Ajbani KK, Rodrigues C. Totally drug-resistant tuberculosis in India. Clin. Infect. Dis. 54(4), 579–581 (2012).
  • Rajbhandary SS, Marks SM, Bock NN. Costs of patients hospitalized for multidrug-resistant tuberculosis. Int. J. Tuberc. Lung Dis. 8(8), 1012–1016 (2004).
  • Chiang CY, Centis R, Migliori GB. Drug-resistant tuberculosis: past, present, future. Respirology 15(3), 413–432 (2010).
  • Amaral L, Kristiansen JE, Abebe LS, Millett W. Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of freshly diagnosed tuberculosis. J.Antimicrob. Chemother. 38(6), 1049–1053 (1996).
  • Ordway D, Viveiros M, Leandro C et al. Clinical concentrations of thioridazine killintracellular multidrug-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47(3), 917–922 (2003).
  • Martins M, Viveiros M, Kristiansen JE, Molnar J, Amaral L. The curative activity of thioridazine on mice infected with Mycobacterium tuberculosis. In Vivo 21(5), 771–775 (2007).
  • van Soolingen D, Hernandez-Pando R, Orozco H et al. The antipsychotic thioridazine shows promising therapeutic activity in a mouse model of multidrug-resistant tuberculosis. PLoS ONE 5(9), pii: e12640 (2010).
  • Udwadia ZF, Sen T, Pinto LM. Safety and efficacy of thioridazine as salvage therapy in Indian patients with XDR-TB. Recent Pat. Antiinfect. Drug Discov. 6(2), 88–91 (2011).
  • Abbate E, Vescovo M, Natiello M et al. Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine. J.Antimicrob. Chemother. 67(2), 473–477 (2012).
  • Amaral L. Totally drug resistant tuberculosis can be treated with thioridazine in combination with antibiotics to which the patient was initially resistant. Biochem. Pharmacol. 39(5), 376–380 (2012).
  • Amaral L, Viveiros M. Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections. Int. J. Antimicrob. Agents 39(5), 376–380 (2012).
  • Amaral L, Molnar J. Potential therapy ofmultidrug-resistant and extremely drug-resistant tuberculosis with thioridazine. In Vivo 26(2), 231–236 (2012).
  • Amaral L, Viveiros M, Molnar J, Kristiansen JE. Effective therapy with the neuroleptic thioridazine as an adjunct to second line of defence drugs, and the potential that thioridazine offers for new patents that cover a variety of “new uses”. Recent Pat. Antiinfect. Drug Discov. 6(2), 84–87 (2011).
  • Amaral L, Martins A, Molnar J et al. Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB. In Vivo 24(4), 409–424 (2010).
  • Amaral L, Boeree MJ, Gillespie SH, Udwadia ZF, van Soolingen D. Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and theneed for global trials is now! Int. J. Antimicrob. Agents 35(6), 524–526 (2010).
  • Amaral L, Martins M, Viveiros M, Molnar J, Kristiansen JE. Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps. Curr. Drug Targets 9(9), 816–819 (2008).
  • Crowle AJ, Douvas GS, May MH. Chlorpromazine: a drug potentially useful for treating mycobacterial infections. Chemotherapy 38(6), 410–419 (1992).
  • Munsiff SS, Ahuja SD, Li J, Driver CR. Public–private collaboration for multidrug-resistant tuberculosis control in New York City. Int. J. Tuberc. Lung Dis. 10(6), 639–648 (2006).
  • Moss AR, Alland D, Telzak E et al. Acity-wide outbreak of a multiple-drug-resistant strain of Mycobacterium tuberculosis in New York. Int. J. Tuberc. Lung Dis. 1(2), 115–121 (1997).
  • Centers for Disease Control and Prevention (CDC). Outbreak of multidrug-resistant tuberculosis at a hospital – New York City, 1991. MMWR Morb. Mortal. Wkly Rep. 42, 427–434 (1993).
  • Centers for Disease Control (CDC). Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons – Florida and New York, 1988–1991. MMWR Morb. Mortal. Wkly Rep. 40, 585–591 (1991).
  • Thanacoody RH. Thioridazine: the good and the bad. Recent Pat. Antiinfect. Drug Discov. 6(2), 92–98 (2011).
  • Martins M, Viveiros M, Ramos J 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 33(5), 479–482 (2009).
  • Martins M, Viveiros M, Amaral L. Inhibitors of Ca2+ and K+ transport enhance intracellular killing of M.tuberculosis by non-killing macrophages. In Vivo 22(1), 69–75 (2008).
  • Amaral L, Martins M, Viveiros M. Phenothiazines as anti-multi-drug resistant tubercular agents. Infect. Disord. Drug Targets 7(3), 257–265 (2007).
  • Martins M, Dastidar SG, Fanning S et al. Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities. Int. J. Antimicrob. Agents 31(3), 198–208 (2008).
  • Martins M, Viveiros M, Amaral L. The TB laboratory of the future: macrophage-based selection of XDR-TB therapeutics. Future Microbiol. 3(2), 135–144 (2008).
  • Martins M, Viveiros M, Couto I, Amaral L. Targeting human macrophages for enhanced killing of intracellular XDR-TB and MDR-TB. Int. J. Tuberc. Lung Dis. 13(5), 569–573 (2009).
  • Reeves EP, Lu H, Jacobs HL et al. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416(6878), 291–297 (2002).
  • Bettencourt M, Amaral L. Enhancement of antibiotic activity against poly-drug resistant Mycobacterium tuberculosis by phenothiazines. Int. J. Antimicrob. Agents 17, 225–228 (2001).
  • Pagès JM, Amaral L. Mechanisms of drug efflux and strategies to combat them: challenging the efflux pump of Gram-negative bacteria. Biochim. Biophys. Acta 1794(5), 826–833 (2009).
  • Pagès JM, Amaral L, Fanning S. An original deal for new molecule: reversal of efflux pump activity, a rational strategy to combat Gram-negative resistant bacteria. Curr. Med. Chem. 18(19), 2969–2980 (2011).
  • Amaral L, Fanning S, Pagès JM. Efflux pumps of Gram-negative bacteria: genetic responses to stress and the modulation of their activity by pH, inhibitors, and phenothiazines. Adv. Enzymol. Relat. AreasMol. Biol. 77, 61–108 (2011).
  • Pasipanodya JG, Gumbo T. A new evolutionary and pharmacokinetic-pharmacodynamic scenario for rapid emergence of resistance to single and multiple anti-tuberculosis drugs. Curr. Opin. Pharmacol. 11(5), 457–463 (2011).
  • da Silva PE, Von Groll A, Martin A, Palomino JC. Efflux as a mechanism for drug resistance in Mycobacterium tuberculosis. FEMS Immunol. Med. Microbiol. 63(1), 1–9 (2011).
  • Dutta NK, Mazumdar K, Dastidar SG, Karakousis PC, Amaral L. New patentable use of an old neuroleptic compound thioridazine to combat tuberculosis: a gene regulation perspective. Recent Pat. Antiinfect. Drug Discov. 6(2), 128–138 (2011).
  • Rodrigues L, Aínsa JA, Amaral L, Viveiros M. Inhibition of drug efflux in mycobacteria with phenothiazines and other putative efflux inhibitors. Recent Pat. Antiinfect. Drug Discov. 6(2), 118–127 (2011).
  • Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria: an update. Drugs 69(12), 1555–1623 (2009).
  • De Rossi E, Aínsa JA, Riccardi G. Role of mycobacterial efflux transporters in drug resistance: an unresolved question. FEMS Microbiol. Rev. 30(1), 36–52 (2006).
  • Viveiros M, Leandro C, Amaral L. Mycobacterial efflux pumps and chemotherapeutic implications. Int. J. Antimicrob. Agents 22(3), 274–278 (2003).
  • Nikaido H. Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria. Semin. Cell Dev. Biol. 12(3), 215–223 (2001).
  • Machado D, Couto I, Perdigão J et al. Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis. PLoS ONE 7(4), e34538 (2012).
  • Rodrigues L, Viveiros M, Sampaio D et al. Thioridazine and chlorpromazine inhibition of ethidium bromide efflux in Mycobacterium avium and Mycobacterium smegmatis. J. Antimicrob. Chem. 61(5), 1076–1082 (2008).
  • Viveiros M, Portugal I, Bettencourt R et al. Isoniazid-induced transient high-level resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 46(9), 2804–2810 (2002).
  • Dutta NK, Mehra S, Kaushal D. AMycobacterium tuberculosis sigma factor network responds to cell-envelope damage by the promising anti-mycobacterial thioridazine. PLoS ONE 5(4), e10069 (2010).
  • Sohaskey C. Latent tuberculosis: is there arole for thioridazine? Recent Pat. Antiinfect. Drug Discov. 6(2), 139–146 (2011).

Website

  • TBTC Study 24. Intermittent Treatment ofTB With Isoniazid Resistance or Intolerance. Center for Disease Control and Prevention; ClinicalTrials.gov Identifier: NCT00023374 (2007). http://clinicaltrials.gov

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.