Skip to main content

Treatment of Drug-Resistant Pulmonary Tuberculosis

  • Chapter
  • First Online:
Diagnostic Imaging of Drug Resistant Pulmonary Tuberculosis

Abstract

Drug-resistant tuberculosis (DR-TB) comprises mainly multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB), rifampicin-susceptible isoniazid-resistant tuberculosis (Hr-TB), and extensively drug-resistant TB (XDR-TB). Compared with drug-susceptible tuberculosis, DR-TB has more incredible treatment difficulty and challenges patients, medical practitioners, and the medical service system. The increasing burden of DR-TB is substantially threatening the global realization of WHO’s strategic goal of “terminating tuberculosis.” Taking Shenzhen, China, as an example, both the ratio of resistance to any drug (34.78%) and multidrug resistance rate (12.06%) in Mycobacterium tuberculosis are high there, as revealed by studies [1]. In order to further prevent DR-TB, WHO issued the first edition of the Integrated Guideline on DR-TB Treatment based on the latest and the most comprehensive evidence-based data and put forward proposals concerning treatment, administration, and care for DR-TB patients. Related policies and guidelines were renewed in June 2020, i.e., Module 4 of Integrated Guideline on Tuberculosis: Treatment of Drug-Resistant Tuberculosis, after this referred to as the Guidance [2].

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

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover 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. Liang F, Zhang P, Deng G, et al. An analysis of drug resistance in 3309 strains of Mycobacterium tuberculosis [J/CD]. Electron J Emerg Inf Dis. 2017;2(1):31–4.

    Google Scholar 

  2. WHO. WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment[M]. Geneva: World Health Organization; 2020.

    Google Scholar 

  3. Gegia M, Winters N, Benedetti A, et al. Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis[J]. Lancet Infect Dis. 2017;17(2):223–34.

    Article  CAS  PubMed  Google Scholar 

  4. Liang F, Weiming L, Huihua Z, et al. A retrospective cohort study of clinical characteristics and treatment regimens of drug-resistant tuberculosis containing isoniazid-resistance[J/CD]. Electron J Emerg Inf Dis. 2021;6(4):306–10.

    Google Scholar 

  5. World Health Organization. WHO treatment guidelines for isoniazid-resistant tuberculosis: supplement to the WHO treatment guidelines for drug-resistant tuberculosis[R]. Geneva: World Health Organization; 2018. p. 1–31.

    Google Scholar 

  6. Fregonese F, Ahuja SD, Akkerman OW, et al. Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis[J]. Lancet Respir Med. 2018;6(4):265–75.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Voogt GR, Schoeman HS. Ototoxicity of aminoglycoside drugs in tuberculosis treatment[J]. S Afr J Commun Disord. 1996;43:3–6.

    CAS  PubMed  Google Scholar 

  8. Gülbay BE, Gürkan OU, Yildiz OA, et al. Side effects due to primary antituberculosis drugs during the initial phase of therapy in 1149 hospitalized patients for tuberculosis[J]. Respir Med. 2006;100(10):1834–42.

    Article  PubMed  Google Scholar 

  9. Bloss E, Kuksa L, Holtz TH, et al. Adverse events related to multidrug-resistant tuberculosis treatment, Latvia, 2000-2004[J]. Int J Tuberc Lung Dis. 2010;14(3):275–81.

    CAS  PubMed  Google Scholar 

  10. World Health Organization. The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs: policy guidance[R]. Geneva: World Health Organization; 2016. https://apps.who.int/iris/bitstream/handle/10665/246131/9789241510561-eng.pdf?sequence=1.

    Google Scholar 

  11. World Health Organization. Rapid communication: molecular assays as initial tests for the diagnosis of tuberculosis and rifampicin resistance[R]. Geneva: World Health Organization; 2020. https://apps.who.int/iris/bitstream/handle/10665/330395/9789240000339-eng.pdf.

    Google Scholar 

  12. Lempens P, Meehan CJ, Vandelannoote K, et al. Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations[J]. Sci Rep. 2018;8(1):3246.

    Article  PubMed  PubMed Central  Google Scholar 

  13. World Health Organization. Guidelines for treatment of drug-susceptible tuberculosis and patient care, 2017 update[R]. Geneva: World Health Organization; 2017. https://apps.who.int/iris/bitstream/handle/10665/255052/9789241550000-eng.pdf?sequence=1.

    Google Scholar 

  14. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: treatment of drug-susceptible tuberculosis[J]. Clin Infect Dis. 2016;63(7):e147–95.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hornik CP, Herring AH, Benjamin DK Jr, et al. Adverse events associated with meropenem versus imipenem/cilastatin therapy in a large retrospective cohort of hospitalized infants[J]. Pediatr Infect Dis J. 2013;32(7):748–53.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Oxlade O, Falzon D, Menzies D. The impact and cost-effectiveness of strategies to detect drug-resistant tuberculosis[J]. Eur Respir J. 2012;39(3):626–34.

    Article  CAS  PubMed  Google Scholar 

  17. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children[R]. Geneva: World Health Organization; 2014. https://apps.who.int/iris/bitstream/handle/10665/112360/9789241548748_eng.pdf?sequence=1.

    Google Scholar 

  18. Zha BS, Nahid P. Treatment of drug-susceptible tuberculosis[J]. Clin Chest Med. 2019;40(4):763–74.

    Article  PubMed  Google Scholar 

  19. Ahmad Khan F, Minion J, Al-Motairi A, et al. An updated systematic review and meta-analysis on the treatment of active tuberculosis in patients with HIV infection[J]. Clin Infect Dis. 2012;55(8):1154–63.

    Article  PubMed  Google Scholar 

  20. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2nd ed. Geneva: World Health Organization; 2016. https://apps.who.int/iris/bitstream/handle/10665/208825/9789241549684_eng.pdf?sequence=1.

    Google Scholar 

  21. Brill MJ, Svensson EM, Pandie M, et al. Confirming model-predicted pharmacokinetic interactions between Bedaquiline and lopinavir/ritonavir or nevirapine in patients with HIV and drug-resistant tuberculosis[J]. Int J Antimicrob Agents. 2017;49(2):212–7.

    Article  CAS  PubMed  Google Scholar 

  22. Svensson EM, Dooley KE, Karlsson MO. Impact of lopinavir-ritonavir or nevirapine on Bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection[J]. Antimicrob Agents Chemother. 2014;58(11):6406–12.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Svensson EM, Aweeka F, Park JG, et al. Model-based estimates of the effects of efavirenz on Bedaquiline pharmacokinetics and suggested dose adjustments for patients coinfected with HIV and tuberculosis[J]. Antimicrob Agents Chemother. 2013;57(6):2780–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cerrone M, Bracchi M, Wasserman S, et al. Safety implications of combined antiretroviral and anti-tuberculosis drugs[J]. Expert Opin Drug Saf. 2020;19(1):23–41.

    Article  CAS  PubMed  Google Scholar 

  25. World Health Organization. WHO consolidated guidelines on drug resistant tuberculosis treatment[R]. Geneva: World Health Organization; 2019. https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?ua=1.

    Google Scholar 

  26. Borisov S, Danila E, Maryandyshev A, et al. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report[J]. Eur Respir J. 2019;54(6):1901522.

    Article  PubMed  Google Scholar 

  27. World Health Organization. Active tuberculosis drug-safety monitoring and management (aDSM). Framework for implementation[R]. Geneva: World Health Organization; 2015. https://apps.who.int/iris/bitstream/handle/10665/204465/WHO_HTM_TB_20.15.28_eng.pdf?sequence=1.

    Google Scholar 

  28. Dooley KE, Miyahara S, von Groote-Bidlingmaier F, et al. Early bactericidal activity of different isoniazid doses for drug resistant TB (INHindsight): a randomized open-label clinical trial[J]. Am J Respir Crit Care Med. 2020;201(11):1416–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Harausz EP, Garcia-Prats AJ, Law S. Treatment and outcomes in children with multidrug-resistant tuberculosis: a systematic review and individual patient data meta-analysis[J]. PLoS Med. 2018;15(7):e1002591.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Thwaites GE, Bhavnani SM, Chau TT, et al. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolone for tuberculous meningitis[J]. Antimicrob Agents Chemother. 2011;55(7):3244–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Donald PR. The chemotherapy of tuberculous meningitis in children and adults[J]. Tuberculosis. 2010;90(6):375–92.

    Article  CAS  PubMed  Google Scholar 

  32. Sun F, Ruan Q, Wang J, et al. Linezolid manifests a rapid and dramatic therapeutic effect for patients with life-threatening tuberculous meningitis[J]. Antimicrob Agents Chemother. 2014;58(10):6297–301.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Akkerman OW, Odish OF, Bolhuis MS, et al. Pharmacokinetics of bedaquiline in cerebrospinal fluid and serum in multidrug-resistant tuberculous meningitis[J]. Clin Infect Dis. 2016;62(4):523–4.

    PubMed  Google Scholar 

  34. Tucker EW, Pieterse L, Zimmerman MD, et al. Delamanid central nervous system pharmacokinetics in tuberculous meningitis in rabbits and humans[J]. Antimicrob Agents Chemother. 2019;63(10):e00913–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Holdiness MR. Cerebrospinal fluid pharmacokinetics of the antituberculosis drugs[J]. Clin Pharmacokinet. 1985;10(6):532–4.

    Article  CAS  PubMed  Google Scholar 

  36. Loveday M, Hughes J, Sunkari B, et al. Maternal and infant outcomes among pregnant women treated for multidrug/rifampicin-resistant tuberculosis in South Africa[J]. Clin Infect Dis. 2021;72(7):1158–68.

    Article  PubMed  Google Scholar 

  37. World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis, 2011 update[R]. Geneva: World Health Organization; 2011. https://www.who.int.

    Google Scholar 

  38. Kurbatova EV, Gammino VM, Bayona J, et al. Frequency and type of microbiological monitoring of multidrug-resistant tuberculosis treatment[J]. Int J Tuberc Lung Dis. 2011;15(11):1553–5.

    Article  CAS  PubMed  Google Scholar 

  39. Mitnick CD, White RA, Lu C, et al. Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method[J]. Eur Respir J. 2016;48(4):1160–70.

    Article  PubMed  PubMed Central  Google Scholar 

  40. World Health Organization. Tuberculosis laboratory biosafety manual[R]. Geneva: World Health Organization; 2012. https://apps.who.int/iris/bitstream/handle/10665/77949/9789241504638_eng.pdf.

    Google Scholar 

  41. World Health Organization. Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis, 27-29 October 2020[R]. Geneva: World Health Organization; 2021.

    Google Scholar 

  42. Conradie F, Diacon AH, Ngubane N, et al. Treatment of highly drug-resistant pulmonary tuberculosis[J]. N Engl J Med. 2020;382(10):893–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sakula A. Selman Waksman (1888-1973), discoverer of streptomycin: a centenary review[J]. Br J Dis Chest. 1988;82(1):23–31.

    Article  CAS  PubMed  Google Scholar 

  44. World Health Organization. Global tuberculosis report 2020 [R]. Geneva: WHO; 2020.

    Google Scholar 

  45. Liangzi Y, Ren Tantan F, Dong X, et al. Bedaquiline in the treatment of pulmonary drug-resistant tuberculosis: safety and efficacy[J/CD]. Electron J Emerg Inf Dis. 2021;6(4):302–5.

    Google Scholar 

  46. Zhao-jing Z, Wei J, Feng-min H, et al. Resistance analysis of extensively drug-resistant Mycobacterium tuberculosis isolates against linezolid[J]. Electron J Emerg Inf Dis. 2017;2(3):160–3.

    Google Scholar 

  47. WHO. The end TB strategy global strategy and targets for tuberculosis prevention, care and control after 2015 [EB/OL]. Geneva: World Health Organization; 2015. https://apps.who.Int/Iris/handle/10665/162760.

    Google Scholar 

  48. World Health Organization. The use of bedaquiline in the treatment of multidrug-resistant tuberculosis: interim policy guidance[M]. Geneva: WHO; 2013.

    Google Scholar 

  49. World Health Organization. The use of delamanid in the treatment of multidrug-resistant tuberculosis in children and adolescents: interim policy guidance [M]. Geneva: WHO; 2016.

    Google Scholar 

  50. Lenaerts AJ, Gruppo V, Marietta KS, et al. Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models [J]. Antimicrob Agents Chemother. 2005;49(6):2294–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zi-hao Z, Zhang W-x, Tian-lei L, et al. Research progress in anti-tuberculosis drugs[J/OL]. J Pharm. 2022;57(4):892–902.

    Google Scholar 

  52. McNeil MR, Brennan PJ. Structure, function and biogenesis of the cell envelope of mycobacteria in relation to bacterial physiology, pathogenesis and drug resistance; some thoughts and possibilities arising from recent structural information[J]. Res Microbiol. 1991;142(4):451.

    Article  CAS  PubMed  Google Scholar 

  53. Journal of Pharmacy. Drug-resistant tuberculosis chemotherapy guidelines (2019)[J]. China Issue Magaz. 2019;41(10):1025–73.

    Google Scholar 

  54. Sotgiu G, Pontali E, Centis R, et al. Delamanid (OPC-67683) for treatment of multi-drug-resistant tuberculosis[J]. Exp Rev Anti-Inf. 2015;13(3):305–15.

    CAS  Google Scholar 

  55. Baptista R, Fazakerley DM, Beckmann M, et al. Untargeted metabolomics reveals a new mode of action of Dretomanid (PA-824)[J]. Sci Rep. 2018;8(1):5084.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Makarov V, Manina G, Mikusova K, et al. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis [J]. Science. 2009;324(5928):801–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tiwari R, Miller PA, Cho S, et al. Syntheses and antituberculosis activity of 1,3-benzothiazinone sulfoxide and sulfone derived from BTZ043[J]. ACS Med Chem Lett. 2015;6(2):128–33.

    Article  CAS  PubMed  Google Scholar 

  58. Shirude PS, Shandil R, Sadler C, et al. Azaindoles: noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo [J]. J Med Chem. 2013;56(23):9701–8.

    Article  CAS  PubMed  Google Scholar 

  59. Hariguchi N, Chen X, Hayashi Y, et al. OPC-167832, a novel carbostyril derivative with potent anti-tuberculosis activity as a DprE1 inhibitor [J]. Antimicrob Agents Chemother. 2020;64(6):e02020.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Sacksteder KA, Protopopova M, Barry CE, et al. Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action[J]. Future Microbiol. 2012;7(7):823–37.

    Article  CAS  PubMed  Google Scholar 

  61. Tahlan K, Wilson R, Kastrinsky DB, et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis [J]. Antimicrob Agents Chemother. 2012;56(4):1797–809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Palencia A, Li X, Bu W, et al. Discovery of novel oral protein synthesis inhibitors of Mycobacterium tuberculosis that target leucyl-tRNA synthetase [J]. Antimicrob Agents Chemother. 2016;60(10):6271–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Barbachyn MR, Hutchinson DK, Brickner SJ, et al. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity [J]. J Med Chem. 1996;39(3):680–5.

    Article  CAS  PubMed  Google Scholar 

  64. Jeong JW, Jung SJ, Lee HH, et al. In vitro and in vivo activities of LCB01-0371, a new oxazolidinone [J]. Antimicrob Agents Chemother. 2010;54(12):5359–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis [J]. Science. 2005;307(5707):223–7.

    Article  CAS  PubMed  Google Scholar 

  66. Sutherland HS, Tong AST, Choi PJ, et al. 3,5-Dialkoxypyridine analogues of Bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel [J]. Bioorg Med Chem. 2019;27(7):1292–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Abrahams KA, Cox JA, Spivey VL, et al. Identification of novel imidazo[1,2-a]pyridine inhibitors targeting M. tuberculosis QcrB [J]. PLoS One. 2012;7(12):e52951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Houslay MD. Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown [J]. Trends Biochem Sci. 2010;35(2):91–100.

    Article  CAS  PubMed  Google Scholar 

  69. Guo J, Lin P, Zhao X, et al. Etazolate abrogates the lipopolysaccharide (LPS)-induced downregulation of the cAMP/pCREB/BDNF signaling, neuroinflammatory response and depressive-like behavior in mice [J]. Neuroscience. 2014;263:1–14.

    Article  CAS  PubMed  Google Scholar 

  70. The Treatment Committee of the Japanese Society for Tuberculosis. Clinical use of rifabutin, a rifamycin-class antibiotic, for the treatment of tuberculosis. Kekkaku. 2011;86(1):43.

    Google Scholar 

  71. Academic Work Committee of China Anti TB Association. Expert consensus on the clinical use of fixed dose compound of anti-tuberculosis drugs [M]. Chin J Anti-tuberculosis. 2020;42(9):885–93.

    Google Scholar 

  72. Tuberculosis Branch of Chinese Medical Association, Preparation Group of Expert Consensus on Linezolid in Anti-tuberculosis Treatment. Expert consensus on linezolid in anti-tuberculosis treatment [J]. Chin J Tuberculosis Respir Dis. 2018;41(1):14–9.

    Google Scholar 

  73. Tuberculosis Branch of Chinese Medical Association. Expert consensus on the clinical application of bedaquiline, a new anti-tuberculosis drug (2020) [J]. Chin J Tuberculosis Respir Dis. 2021;44(2):81–7.

    Google Scholar 

  74. Diacon AH, Pym A, Grobusch MP, et al. Multidrug-resistant tuberculosis and culture conversion with Bedaquiline[J]. N Engl J Med. 2014;371(8):723–32.

    Article  PubMed  Google Scholar 

  75. World Health Organization. Interim policy guidance for the use of Delamanid in the treatment of MDR-TB[R]. WHO/HTM/TB/2014.23. Geneva: World Health Organization; 2014.

    Google Scholar 

  76. National Association for the Prevention of Tuberculosis, Tuberculosis Prevention and Control Center under Chinese Center for Disease Control and Prevention. Recommendation of application of Pretomanid (PA-824) to the treatment of multidrug resistant tuberculosis [J]. Chin J Antituberculosis. 2022;44(1):38–43.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 People's Medical Publishing House, PR of China

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Deng, Gf. et al. (2023). Treatment of Drug-Resistant Pulmonary Tuberculosis. In: Lu, PX., Lu, Hz., Yi, Yx. (eds) Diagnostic Imaging of Drug Resistant Pulmonary Tuberculosis. Springer, Singapore. https://doi.org/10.1007/978-981-99-8339-1_15

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-8339-1_15

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-8338-4

  • Online ISBN: 978-981-99-8339-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics