Bedaquiline: a new weapon against MDR and XDR-TB

Authors

  • Harmanjit Singh Department of Pharmacology,PGIMER, Chandigarh, India
  • Navreet Kaur Natt Medical Officer (TB-control), District TB Hospital, Amritsar, Punjab, India
  • Nipunjot Garewal Department of Pharmacology, Punjab Institute of Medical Sciences, Jalandhar,Punjab, India
  • Pugazhenthan T. Department of Pharmacology,PGIMER, Chandigarh, India

Keywords:

MDR, XDR, TB, Bedaquiline, TMC-207, Mycobacteria

Abstract

Multidrug-resistant tuberculosis (MDR-TB) is a global public health problem. It requires treatment with combination therapy consisting of four to six drugs including combinations of bactericidal and bacteriostatic drugs, usually for a period of 2 years. There is alarming rise in MDR and XDR-TB all over the world and better treatment options are needed to control the global MDR-TB and XDR-TB epidemic. Drugs which can shorten the treatment duration and which are free from serious adverse effects are urgently needed. Bedaquiline (TMC-207) is a newly FDA approved anti-TB drug, having unique mechanism of action i.e. causes inhibition of the proton pump activity of the ATP synthase in M. tuberculosis and targets the energy metabolism. It is found to active within macrophages, and is a promising agent in shortening the duration of anti- TB treatment. It is metabolized by CYP3A4, so interactions with inducers and inhibitors of this enzyme are expected. It has shown promising results in preclinical and clinical studies and it seems to be a good option for MDR and XDR-TB. Adverse effects reported in various studies were of mild nature except nausea which was the most commonly associated. Few cases of prolongation of QT intervals were reported, so it demands careful monitoring and use of bedaquiline as a reserve drug for patients in whom conventional regimens are not effective. Currently it is approved as part of combination therapy in adults of ≥18 year with pulmonary MDR-TB. Long term studies are needed to explore its full safety profile.

References

Multidrug and extensively drug-resistant TB, WHO, 2010 Global Report. Available at http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf. Accessed 19 Jan 2013.

Falzon D, Jaramillo E, Schünemann HJ, Arentz M, Bauer M, Bayona J, et al. WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update. Eur Respir J 2011;38:516-28.

Diel R, Rutz S, Castell S, Schaberg T. Tuberculosis: cost of illness in Germany. Eur Respir J 2012;40:143-51.

Loddenkemper R, Sotgiu G, Mitnick CD. Cost of tuberculosis in the era of multidrug resistance: will it become unaffordable? Eur Respir J 2012;40:9-11.

MDR- TB, 2012 update. Available at http://www.who.int/tb/publications/ MDRFactSheet2012.pdf. Accessed 22 Jan 2013.

Sotgiu G, Ferrara G, Matteelli A, Richardson MD, Centis R, Toungoussova O et al. Epidemiology and clinical management of XDR-TB: a systematic review by TBNET. Eur Respir J 2009;33:871-81.

Jacobson KR, Tierney DB, Jeon CY, Mitnick CD, Murray MB. Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis. Clin Infect Dis 2010;51:6-14.

Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, et al. Extensively drug-resistant tuberculosis as a cause of death in patients coinfected with tuberculosis and HIV in a rural area of South Africa. Lancet 2006;368:1575-80.

Mitchison DA. Role of individual drugs in the chemotherapy of tuberculosis. Int J Tuberc Lung Dis 2000;4:796-806.

World Health Organization. 2011. Global tuberculosis control 2011. Available at: http://www.who.int/tb/publications/2011/en/index.html. Accessed 19 Jan 2013.

Field SK, Fisher D, Jarand JM, Cowie RL. New treatment options for multidrug-resistant tuberculosis. Ther Adv Respir Dis 2012;6:255-268.

Matteelli A, Carvalho AC, Dooley KE, Kritski A. TMC207: the first compound of a new class of potent anti-tuberculosis drugs. Future Microbiol 2010;5:849-58.

Ahmad S. New Perspectives in the Diagnosis and Treatment of Tuberculosis. J Bacteriol Parasitol 2012;3:e114. doi:10.4172/2155-9597.1000e114.

Andries K, Verhasselt P, Guillemont J. E. G, Gohlmann HW. Neefs JM, Winkler H, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005;307:223-7.

Gumbo T. TMC-207 (R207910). In: Bruten L, Chabner BA, Knollmann BC, editors. Goodman and Gillman’s The Pharmacological Basis of Therapeutics. 12th edn. New York, NY: McGraw Hill Companies; 2011:1561.

Van Heeswijk, R, Lachaert R, Leopold L, DeBeule K, McNeeley D. The effect of CYP3A4 inhibition on the clinical pharmacokinetics of TMC207. Presented at: the 38th Union World Conference on Lung Health; Cape Town, South Africa. 8-12 November 2007; Poster PS-71358-71311.

Huitric E, Verhasselt P, Andries K, Hoffner SE. In vitro antimycobacterial spectrum of a diarylquinoline ATP-synthase inhibitor. Antimicrob Agents Chemother 2007;51:4202-4.

Shi L, Sohaskey CD, Kana BD, Dawes S, North RJ, Mizrahi V, et al. Changes in energy metabolism of Mycobacterium tuberculosis in mouse lung and in vitro conditions affecting aerobic respiration. Proc Natl Acad Sci U S A 2005;102:15629-34.

Koul A, Vranckx L, Dendouga N, Balemans W, Van den Wyngaert I, Vergauwen K, et al. Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis. J Biol Chem 2008;283:25273-80.

Petrella S, Cambau E, Chauffour A, Andries K, Jarlier V, Sougakoff W. Genetic basis for natural and acquired resistance of the diaryquinoline R207910 in mycobacteria. Antimicrob Agents Chemother 2006;50:2853-6.

Ibrahim M, Truffot-Pernot C, Andries K, Jarlier V, Veziris N. Sterilizing activity of R207910 (TMC207) - containing regimens in the murine model of tuberculosis. Am J Respir Crit Care Med 2009;180:553-7.

Lenaerts AJ, Hoff D, Aly S, Ehlers S, Andries K, Cantarero L, et al. Location of persisting mycobacteria in a Guinea pig model of tuberculosis revealed by R207910. Antimicrob Agents Chemother 2007;51:3338-45.

Lounis N, Veziris N, Chauffour A, Truffot-Pernot C, Andries K, Jarlier V. Combinations of R207910 with drugs used to treat multidrug-resistant tuberculosis have the potential to shorten treatment duration. Antimicrob Agents Chemother 2006;50:3543-7.

Zhang T, Li SY, Williams KN, Andries K, Nuermberger EL. Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med 2011;184:732-7.

Veziris N, Ibrahim M, Lounis N, Andries K, Jarlier V. Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis. PLoS One 2011;6:e17556.

Rustomjee R, Diacon AH, Allen J, Venter A, Reddy C, Patientia RF et al. Early bactericidal activity and pharmacokinetics of the dairylquinoline TMC207 in treatment of pulmonary tuberculosis. Antimicrob Agents Chemother 2008;52:2831-5.

Diacon AH, Pym AP, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med 2009;360:2397-405.

Diacon AH, Donald PR, Pym A, Grobusch M, Patientia RF, et al. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob Agents Chemother 2012;56:3271-6.

Wallis RS, Jakubiec W, Mitton-Fry M, Ladutko L, Campbell S, Paige D et al. Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid), TMC207, PA-824, SQ109, and pyrazinamide. PLoS One 2012;7:e30479.

Sirturo (bedaquiline fumarate). Available at http://dailymed.nlm.nih.gov/dailymed/ lookup.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e.pdf. Accessed 20 Jan 2013.

Bedaquiline. Available at http://reference.medscape.com/drug/sirturo-bedaquiline-999799#5. Accessed 20 Jan 2013.

FDA approves first drug to treat multi-drug resistant tuberculosis. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm. Accessed 19 Jan 2013.

WHO to convene expert meeting on the use of bedaquiline for MDR-TB treatment. Available at http://www.tbonline.info/posts/2013/1/7/who-convene-expert-meeting-use-bedaquiline-mdr-tb-/. Accessed 21 Jan 2013.

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Published

2017-01-30

How to Cite

Singh, H., Natt, N. K., Garewal, N., & T., P. (2017). Bedaquiline: a new weapon against MDR and XDR-TB. International Journal of Basic & Clinical Pharmacology, 2(2), 96–102. Retrieved from https://www.ijbcp.com/index.php/ijbcp/article/view/1221

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Section

Review Articles