Skip to main content

Emerging Therapies

  • Chapter
  • First Online:
Handbook of Tuberculosis

Abstract

Despite the tremendous efficacy of the treatment of tuberculosis (TB) which can cure the disease in 6 months and resulted in the dramatic reduction of patient sufferings from TB, the success of TB treatment has been hampered by the development of resistance to existing drugs in numerous part of the world [1]. This, in turn, has reactivated research on drugs active against TB (Table 7.1), on vaccines safer and more efficacious than BCG, and on host-directed therapies. The current chapter is providing a summary of the state of the art in these fields [2].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. WHO. Global tuberculosis report. Geneva, Switzerland; 2014.

    Google Scholar 

  2. Zumla A, Chakaya J, Centis R, D’Ambrosio L, Mwaba P, Bates M, et al. Tuberculosis treatment and management--an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med. 2015;3(3):220–34.

    Article  PubMed  Google Scholar 

  3. Pethe K, Bifani P, Jang J, Kang S, Park S, Ahn S, et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat Med. 2013;19(9):1157–60.

    Article  CAS  PubMed  Google Scholar 

  4. Andries K, Verhasselt P, Guillemont J, Gohlmann HW, Neefs JM, Winkler H, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005;307(5707):223–7.

    Article  CAS  PubMed  Google Scholar 

  5. Makarov V, Manina G, Mikusova K, Mollmann U, Ryabova O, Saint-Joanis B, et al. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science. 2009;324(5928):801–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Makarov V, Lechartier B, Zhang M, Neres J, van der Sar AM, Raadsen SA, et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol Med. 2014;6(3):372–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. FDA U. 2012 [updated 15 March 2015]. December 31, 2012 [United States Food and Drug Administration]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm.

  8. FDA U. Briefing Package: NDA 204–384. 2012.

    Google Scholar 

  9. EMA. EMA/794261/2013. 2013;20 December 2013.

    Google Scholar 

  10. WHO. The use of bedaquiline in the treatment of multidrug-resistant tuberculosis. Interim policy guidance. Geneva; 2013.

    Google Scholar 

  11. Andries K, Gevers T, Lounis N. Bactericidal potencies of new regimens are not predictive of their sterilizing potencies in a murine model of tuberculosis. Antimicrob Agents Chemother. 2010;54(11):4540–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ibrahim M, Andries K, Lounis N, Chauffour A, Truffot-Pernot C, Jarlier V, et al. Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis. Antimicrob Agents Chemother. 2007;51(3):1011–5.

    Article  CAS  PubMed  Google Scholar 

  13. 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(6):553–7.

    Article  CAS  PubMed  Google Scholar 

  14. Lounis N, Gevers T, Van Den Berg J, Andries K. Impact of the interaction of R207910 with rifampin on the treatment of tuberculosis studied in the mouse model. Antimicrob Agents Chemother. 2008;52(10):3568–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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(11):3543–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rouan MC, Lounis N, Gevers T, Dillen L, Gilissen R, Raoof A, et al. Pharmacokinetics and pharmacodynamics of TMC207 and its N-desmethyl metabolite in a murine model of tuberculosis. Antimicrob Agents Chemother. 2012;56(3):1444–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 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(3), e17556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rustomjee R, Diacon AH, Allen J, Venter A, Reddy C, Patientia RF, et al. Early bactericidal activity and pharmacokinetics of the diarylquinoline TMC207 in treatment of pulmonary tuberculosis. Antimicrob Agents Chemother. 2008;52(8):2831–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, et al. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet. 2012;380(9846):986–93.

    Article  CAS  PubMed  Google Scholar 

  20. Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, et al. Bactericidal activity of pyrazinamide and clofazimine alone and in combinations with pretomanid and bedaquiline. Am J Respir Crit Care Med. 2015;191(8):943–53.

    Article  CAS  PubMed  Google Scholar 

  21. Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009;360(23):2397–405.

    Article  CAS  PubMed  Google Scholar 

  22. Diacon AH, Donald PR, Pym A, Grobusch M, Patientia RF, Mahanyele R, 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(6):3271–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014;371(8):723–32.

    Article  PubMed  Google Scholar 

  24. Guglielmetti L, Le Du D, Jachym M, Henry B, Martin D, Caumes E, et al. Compassionate use of bedaquiline for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis: interim analysis of a French cohort. Clin Infect Dis. 2015;60(2):188–94.

    Article  CAS  PubMed  Google Scholar 

  25. Matsumoto M, Hashizume H, Tomishige T, Kawasaki M, Tsubouchi H, Sasaki H, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med. 2006;3(11), e466.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Diacon AH, Dawson R, Hanekom M, Narunsky K, Venter A, Hittel N, et al. Early bactericidal activity of delamanid (OPC-67683) in smear-positive pulmonary tuberculosis patients. Int J Tuberc Lung Dis. 2011;15(7):949–54.

    Article  CAS  PubMed  Google Scholar 

  27. Gler MT, Skripconoka V, Sanchez-Garavito E, Xiao H, Cabrera-Rivero JL, Vargas-Vasquez DE, et al. Delamanid for multidrug-resistant pulmonary tuberculosis. N Engl J Med. 2012;366(23):2151–60.

    Article  CAS  PubMed  Google Scholar 

  28. Gupta R, Geiter LJ, Wells CD, Gao M, Cirule A, Xiao H. Delamanid for extensively drug-resistant tuberculosis. N Engl J Med. 2015;373(3):291–2.

    Article  CAS  PubMed  Google Scholar 

  29. Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000;405(6789):962–6.

    Article  CAS  PubMed  Google Scholar 

  30. Ginsberg AM, Laurenzi MW, Rouse DJ, Whitney KD, Spigelman MK. Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects. Antimicrob Agents Chemother. 2009;53(9):3720–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tyagi S, Nuermberger E, Yoshimatsu T, Williams K, Rosenthal I, Lounis N, et al. Bactericidal activity of the nitroimidazopyran PA-824 in a murine model of tuberculosis. Antimicrob Agents Chemother. 2005;49(6):2289–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nuermberger E, Tyagi S, Tasneen R, Williams KN, Almeida D, Rosenthal I, et al. Powerful bactericidal and sterilizing activity of a regimen containing PA-824, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. Antimicrob Agents Chemother. 2008;52(4):1522–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dawson R, Diacon AH, Everitt D, van Niekerk C, Donald PR, Burger DA, et al. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis. Lancet. 2015;385(9979):1738–47.

    Article  CAS  PubMed  Google Scholar 

  34. Kmentova I, Sutherland HS, Palmer BD, Blaser A, Franzblau SG, Wan B, et al. Synthesis and structure-activity relationships of aza- and diazabiphenyl analogues of the antitubercular drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1, 3]oxazine (PA-824). J Med Chem. 2010;53(23):8421–39.

    Article  CAS  PubMed  Google Scholar 

  35. Upton AM, Cho S, Yang TJ, Kim Y, Wang Y, Lu Y, et al. In vitro and in vivo activities of the nitroimidazole TBA-354 against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015;59(1):136–44.

    Article  CAS  PubMed  Google Scholar 

  36. Tasneen R, Williams K, Amoabeng O, Minkowski A, Mdluli KE, Upton AM, et al. Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis. Antimicrob Agents Chemother. 2015;59(1):129–35.

    Article  PubMed  Google Scholar 

  37. Barbachyn MR, Hutchinson DK, Brickner SJ, Cynamon MH, Kilburn JO, Klemens SP, et al. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J Med Chem. 1996;39(3):680–5.

    Article  CAS  PubMed  Google Scholar 

  38. Shaw KJ, Barbachyn MR. The oxazolidinones: past, present, and future. Ann N Y Acad Sci. 2011;1241:48–70.

    Article  CAS  PubMed  Google Scholar 

  39. Stalker DJ, Jungbluth GL. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial. Clin Pharmacokinet. 2003;42(13):1129–40.

    Article  CAS  PubMed  Google Scholar 

  40. Huang TS, Liu YC, Sy CL, Chen YS, Tu HZ, Chen BC. In vitro activities of linezolid against clinical isolates of Mycobacterium tuberculosis complex isolated in Taiwan over 10 years. Antimicrob Agents Chemother. 2008;52(6):2226–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dietze R, Hadad DJ, McGee B, Molino LP, Maciel EL, Peloquin CA, et al. Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis. Am J Respir Crit Care Med. 2008;178(11):1180–5.

    Article  PubMed  PubMed Central  Google Scholar 

  42. McKee EE, Ferguson M, Bentley AT, Marks TA. Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob Agents Chemother. 2006;50(6):2042–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Migliori GB, Eker B, Richardson MD, Sotgiu G, Zellweger JP, Skrahina A, et al. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur Respir J. 2009;34(2):387–93.

    Article  CAS  PubMed  Google Scholar 

  44. Yew WW, Chau CH, Wen KH. Linezolid in the treatment of ‘difficult’ multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2008;12(3):345–6.

    CAS  PubMed  Google Scholar 

  45. Lee M, Cho SN, Barry 3rd CE, Song T, Kim Y, Jeong I. Linezolid for XDR-TB – final study outcomes. N Engl J Med. 2015;373(3):290–1.

    Article  CAS  PubMed  Google Scholar 

  46. Lee M, Lee J, Carroll MW, Choi H, Min S, Song T, et al. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012;367(16):1508–18.

    Article  CAS  PubMed  Google Scholar 

  47. Cox H, Ford N. Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2012;16(4):447–54.

    Article  CAS  PubMed  Google Scholar 

  48. Chang KC, Yew WW, Cheung SW, Leung CC, Tam CM, Chau CH, et al. Can intermittent dosing optimize prolonged linezolid treatment of difficult multidrug-resistant tuberculosis? Antimicrob Agents Chemother. 2013;57(7):3445–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Williams KN, Stover CK, Zhu T, Tasneen R, Tyagi S, Grosset JH, et al. Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model. Antimicrob Agents Chemother. 2009;53(4):1314–9.

    Article  CAS  PubMed  Google Scholar 

  50. Williams KN, Brickner SJ, Stover CK, Zhu T, Ogden A, Tasneen R, et al. Addition of PNU-100480 to first-line drugs shortens the time needed to cure murine tuberculosis. Am J Respir Crit Care Med. 2009;180(4):371–6.

    Article  CAS  PubMed  Google Scholar 

  51. 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(1), e30479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wallis RS, Dawson R, Friedrich SO, Venter A, Paige D, Zhu T, et al. Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLoS One. 2014;9(4), e94462.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Vera-Cabrera L, Gonzalez E, Rendon A, Ocampo-Candiani J, Welsh O, Velazquez-Moreno VM, et al. In vitro activities of DA-7157 and DA-7218 against Mycobacterium tuberculosis and Nocardia brasiliensis. Antimicrob Agents Chemother. 2006;50(9):3170–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Urbina O, Ferrandez O, Espona M, Salas E, Ferrandez I, Grau S. Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections. Drug Des Devel Ther. 2013;7:243–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA. 2013;309(6):559–69.

    Article  CAS  PubMed  Google Scholar 

  56. Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014;14(8):696–705.

    Article  CAS  PubMed  Google Scholar 

  57. Johnson JL, Hadad DJ, Boom WH, Daley CL, Peloquin CA, Eisenach KD, Jankus DD, Debanne SM, Charlebois ED, Maciel E, Palaci M, Dietze R. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2006;10(6):605–12.

    Google Scholar 

  58. Nuermberger EL, Yoshimatsu T, Tyagi S, O’Brien RJ, Vernon AN, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med. 2004;169(3):421–6.

    Google Scholar 

  59. Ji B, Lounis N, Maslo C, Truffot-Pernot C, Bonnafous P, Grosset J. In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1998;42(8):2066–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Nuermberger EL, Yoshimatsu T, Tyagi S, O’Brien RJ, Vernon AN, Chaisson RE, et al. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med. 2004;169(3):421–6.

    Article  PubMed  Google Scholar 

  61. Pletz MW, De Roux A, Roth A, Neumann KH, Mauch H, Lode H. Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study. Antimicrob Agents Chemother. 2004;48(3):780–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Dorman SE, Johnson JL, Goldberg S, Muzanye G, Padayatchi N, Bozeman L, et al. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. Am J Respir Crit Care Med. 2009;180(3):273–80.

    Article  CAS  PubMed  Google Scholar 

  63. Conde MB, Efron A, Loredo C, De Souza GR, Graca NP, Cezar MC, et al. Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial. Lancet. 2009;373(9670):1183–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Rustomjee R, Lienhardt C, Kanyok T, Davies GR, Levin J, Mthiyane T, et al. A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2008;12(2):128–38.

    CAS  PubMed  Google Scholar 

  65. Merle CS, Fielding K, Sow OB, Gninafon M, Lo MB, Mthiyane T, et al. A four-month gatifloxacin-containing regimen for treating tuberculosis. N Engl J Med. 2014;371(17):1588–98.

    Article  PubMed  Google Scholar 

  66. Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014;371(17):1577–87.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Jindani A, Harrison TS, Nunn AJ, Phillips PP, Churchyard GJ, Charalambous S, et al. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014;371(17):1599–608.

    Article  PubMed  PubMed Central  Google Scholar 

  68. WHO. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva; 2014.

    Google Scholar 

  69. Walsh C. Antibiotics: actions, origins, resistance. Walsh C, editor. Washington, DC: ASM Press; 2003. p. 23–49.

    Google Scholar 

  70. Hamad B. The antibiotics market. Nat Rev Drug Discov. 2010;9(9):675–6.

    Article  CAS  PubMed  Google Scholar 

  71. Hugonnet JE, Blanchard JS. Irreversible inhibition of the Mycobacterium tuberculosis beta-lactamase by clavulanate. Biochemistry. 2007;46(43):11998–2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hugonnet JE, Tremblay LW, Boshoff HI, Barry 3rd CE, Blanchard JS. Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis. Science. 2009;323(5918):1215–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lavollay M, Arthur M, Fourgeaud M, Dubost L, Marie A, Veziris N, et al. The peptidoglycan of stationary-phase Mycobacterium tuberculosis predominantly contains cross-links generated by L,D-transpeptidation. J Bacteriol. 2008;190(12):4360–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gupta R, Lavollay M, Mainardi JL, Arthur M, Bishai WR, Lamichhane G. The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin. Nat Med. 2010;16(4):466–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Goffin C, Ghuysen JM. Biochemistry and comparative genomics of SxxK superfamily acyltransferases offer a clue to the mycobacterial paradox: presence of penicillin-susceptible target proteins versus lack of efficiency of penicillin as therapeutic agent. Microbiol Mol Biol Rev. 2002;66(4):702–38.

    Google Scholar 

  76. Horita Y, Maeda S, Kazumi Y, Doi N. In vitro susceptibility of Mycobacterium tuberculosis isolates to an oral carbapenem alone or in combination with beta-lactamase inhibitors. Antimicrob Agents Chemother. 2014;58(11):7010–4.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Hazra S, Xu H, Blanchard JS. Tebipenem, a new carbapenem antibiotic, is a slow substrate that inhibits the beta-lactamase from Mycobacterium tuberculosis. Biochemistry. 2014;53(22):3671–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Dhar N, Dubee V, Ballell L, Cuinet G, Hugonnet JE, Signorino-Gelo F, et al. Rapid cytolysis of Mycobacterium tuberculosis by faropenem, an orally bioavailable beta-lactam antibiotic. Antimicrob Agents Chemother. 2015;59(2):1308–19.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Kaushik A, Makkar N, Pandey P, Parrish N, Singh U, Lamichhane G. Carbapenems and rifampicin exhibit synergy against Mycobacterium tuberculosis and Mycobacterium abscessus. Antimicrob Agents Chemother. 2015;59(10):6561–7.

    Google Scholar 

  80. Keener AB. Oldie but goodie: repurposing penicillin for tuberculosis. Nat Med. 2014;20(9):976–8.

    Article  CAS  PubMed  Google Scholar 

  81. Dooley KE, Bliven-Sizemore EE, Weiner M, Lu Y, Nuermberger EL, Hubbard WC, et al. Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers. Clin Pharmacol Ther. 2012;91(5):881–8.

    Article  CAS  PubMed  Google Scholar 

  82. Dorman SE, Savic RM, Goldberg S, Stout JE, Schluger N, Muzanyi G, et al. Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial. Am J Respir Crit Care Med. 2015;191(3):333–43.

    Article  CAS  PubMed  Google Scholar 

  83. Barry VC, Conalty ML. The antimycobacterial activity of B 663. Lepr Rev. 1965;36:3–7.

    CAS  PubMed  Google Scholar 

  84. Lounis N, Gevers T, Van den Berg J, Vranckx L, Andries K. ATP synthase inhibition of Mycobacterium avium is not bactericidal. Antimicrob Agents Chemother. 2009;53(11):4927–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Chaisson RE, Keiser P, Pierce M, Fessel WJ, Ruskin J, Lahart C, et al. Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection. AIDS. 1997;11(3):311–7.

    Article  CAS  PubMed  Google Scholar 

  86. Shafran SD, Singer J, Zarowny DP, Phillips P, Salit I, Walmsley SL, et al. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group. N Engl J Med. 1996;335(6):377–83.

    Article  CAS  PubMed  Google Scholar 

  87. Aung KJ, Van Deun A, Declercq E, Sarker MR, Das PK, Hossain MA, et al. Successful ‘9-month Bangladesh regimen’ for multidrug-resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis. 2014;18(10):1180–7.

    Article  CAS  PubMed  Google Scholar 

  88. Kuaban C, Noeske J, Rieder HL, Ait-Khaled N, Abena Foe JL, Trebucq A. High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon. Int J Tuberc Lung Dis. 2015;19(5):517–24.

    Article  CAS  PubMed  Google Scholar 

  89. Tang S, Yao L, Hao X, Liu Y, Zeng L, Liu G, et al. Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective, multicenter, randomized controlled study in China. Clin Infect Dis. 2015;60(9):1361–7.

    PubMed  Google Scholar 

  90. Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010;182(5):684–92.

    Article  PubMed  Google Scholar 

  91. Grosset JH, Tyagi S, Almeida DV, Converse PJ, Li SY, Ammerman NC, et al. Assessment of clofazimine activity in a second-line regimen for tuberculosis in mice. Am J Respir Crit Care Med. 2013;188(5):608–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Tyagi S, Ammerman NC, Li SY, Adamson J, Converse PJ, Swanson RV, et al. Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis. Proc Natl Acad Sci U S A. 2015;112(3):869–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Mangtani P, Abubakar I, Ariti C, Beynon R, Pimpin L, Fine PE, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis. 2014;58(4):470–80.

    Article  PubMed  Google Scholar 

  94. Hokey DA, Ginsberg A. The current state of tuberculosis vaccines. Human Vaccines Immunother. 2013;9(10):2142–6.

    Article  CAS  Google Scholar 

  95. Tameris M, Geldenhuys H, Luabeya AK, Smit E, Hughes JE, Vermaak S, et al. The candidate TB vaccine, MVA85A, induces highly durable Th1 responses. PLoS One. 2014;9(2), e87340.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013;381(9871):1021–8.

    Article  CAS  PubMed  Google Scholar 

  97. Kaufmann SH. Tuberculosis vaccine development: strength lies in tenacity. Trends Immunol. 2012;33(7):373–9.

    Article  CAS  PubMed  Google Scholar 

  98. Kaufmann SH, Lange C, Rao M, Balaji KN, Lotze M, Schito M, et al. Progress in tuberculosis vaccine development and host-directed therapies--a state of the art review. Lancet Respir Med. 2014;2(4):301–20.

    Article  CAS  PubMed  Google Scholar 

  99. Wallis RS, Hafner R. Advancing host-directed therapy for tuberculosis. Nat Rev Immunol. 2015;15(4):255–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jacques H. Grosset .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Lamichhane, G., Grosset, J.H. (2017). Emerging Therapies. In: Grosset, J., Chaisson, R. (eds) Handbook of Tuberculosis. Adis, Cham. https://doi.org/10.1007/978-3-319-26273-4_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26273-4_7

  • Published:

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-26271-0

  • Online ISBN: 978-3-319-26273-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics