Yeungnam Univ J Med.  2020 Oct;37(4):277-285. 10.12701/yujm.2020.00626.

Diagnosis and treatment of multidrug-resistant tuberculosis

Affiliations
  • 1Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea

Abstract

Tuberculosis (TB) is still a major health problem worldwide. Especially, multidrug-resistant TB (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, is a barrier in the treatment of TB. Globally, approximately 3.4% of new TB patients and 20% of the patients with a history of previous treatment for TB were diagnosed with MDR-TB. The treatment of MDR-TB requires medications for a long duration (up to 20–24 months) with less effective and toxic second-line drugs and has unfavorable outcomes. However, treatment outcomes are expected to improve due to the introduction of a new agent (bedaquiline), repurposed drugs (linezolid, clofazimine, and cycloserine), and technological advancement in rapid drug sensitivity testing. The World Health Organization (WHO) released a rapid communication in 2018, followed by consolidated guidelines for the treatment of MDR-TB in 2019 based on clinical trials and an individual patient data meta-analysis. In these guidelines, the WHO suggested reclassification of second-line anti-TB drugs and recommended oral treatment regimens that included the new and repurposed agents. The aims of this article are to review the treatment strategies of MDR-TB based on the 2019 WHO guidelines regarding the management of MDR-TB and the diagnostic techniques for detecting resistance, including phenotypic and molecular drug sensitivity tests.

Keyword

Diagnosis; Multidrug-resistant tuberculosis; Therapeutics

Cited by  1 articles

Advances in the science and treatment of respiratory diseases
Jin Hong Chung
Yeungnam Univ J Med. 2020;37(4):251-252.    doi: 10.12701/yujm.2020.00661.


Reference

References

1. World Health Organization. Global health estimates 2016: deaths by cause, age, sex, by country and by region, 2000-2016 [Internet]. Geneva: World Health Organization;2018. [cited 2020 Jul 14]. https://www.who.int/healthinfo/global_burden_disease/estimates/en/.
2. World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment [Internet]. Geneva: World Health Organization;2019. [cited 2020 Jul 14]. https://www.who.int/tb/publications/2019/consolidated-guidelines-drug-resistant-TB-treatment/en/.
3. World Health Organization. Global tuberculosis report 2015 [Internet]. 20th ed. Geneva: World Health Organization;2015. [cited 2020 Jul 14]. https://apps.who.int/iris/handle/10665/191102.
4. World Health Organization. Global tuberculosis report 2019 [Internet]. Geneva: World Health Organization;2019. [cited 2020 Jul 14]. https://www.who.int/tb/publications/global_report/en/.
5. World Health Organization. Treatment guidelines for drug-resistant tuberculosis, 2016 update [Internet]. Geneva: World Health Organization;2016. [cited 2020 Jul 14]. https://www.who.int/publications/i/item/9789241549639.
6. David HL. Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl Microbiol. 1970; 20:810–4.
Article
7. Kim SJ. Drug-susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J. 2005; 25:564–9.
Article
8. Zhang Y, Yew WW. Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015. Int J Tuberc Lung Dis. 2015; 19:1276–89.
Article
9. Kendall EA, Fofana MO, Dowdy DW. Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med. 2015; 3:963–72.
Article
10. Canetti G, Froman S, Grosset J, Hauduroy P, Langerova M, Mahler HT, et al. Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull World Health Organ. 1963; 29:565–78.
11. World Health Oraganization. Guidelines for surveillance of drug resistance in tuberculosis [Internet]. 4th ed. Geneva: World Health Oraganization;2009. [cited 2020 Jul 14]. https://www.who.int/tb/publications/surveillance_guidelines/en/.
12. CanettI G, Rist N, Grosset J. Measurement of sensitivity of the tuberculous bacillus to antibacillary drugs by the method of proportions. Methodology, resistance criteria, results and interpretation. Rev Tuberc Pneumol (Paris). 1963; 27:217–72.
13. Schaberg T, Reichert B, Schülin T, Lode H, Mauch H. Rapid drug susceptibility testing of Mycobacterium tuberculosis using conventional solid media. Eur Respir J. 1995; 8:1688–93.
14. World Health Organization. Use of liquid TB culture and drug susceptibility testing (DST) in low and medium income setting. Summary report of the Expert Group Meeting on the use of liquid culture media [Internet]. Geneva: World Health Organization;2007. [cited 2018 Dec 18]. https://www.who.int/tb/laboratory/use_of_liquid_tb_culture_summary_report.pdf?ua=1.
15. Koh WJ, Ko Y, Kim CK, Park KS, Lee NY. Rapid diagnosis of tuberculosis and multidrug resistance using a MGIT 960 system. Ann Lab Med. 2012; 32:264–9.
Article
16. Coll F, McNerney R, Preston MD, Guerra-Assunção JA, Warry A, Hill-Cawthorne G, et al. Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences. Genome Med. 2015; 7:51.
Article
17. World Health Organization. Molecular line probe assays for rapid screening of patients at risk of multidrug-resistant tuberculosis (MDR-TB) [Internet]. Geneva: World Health Organization;2008. [cited 2020 Jul 14]. https://www.who.int/tb/laboratory/line_probe_assays/en/.
18. World Health Organization. The use of molecular line probe assays for the detection of resistance to isoniazid and rifampicin [Internet]. Geneva: World Health Organization;2016. [cited 2020 Jul 14]. https://www.who.int/tb/publications/molecular-test-resistance/en/.
19. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis–rapid diagnostics for tuberculosis detection [Internet]. Geneva: World Health Organization;2020. [cited 2020 Jul 14]. https://www.who.int/publications/i/item/who-consolidated-guidelines-on-tuberculosis-module-3-diagnosis---rapid-diagnostics-for-tuberculosis-detection.
20. Hillemann D, Rüsch-Gerdes S, Richter E. Evaluation of the GenoType MTBDRplus assay for rifampin and isoniazid susceptibility testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol. 2007; 45:2635–40.
Article
21. Hain Lifescience GmbH. GenoType MTBDRplus, ver. 2.0. Instructions for use (IFU-304A-06) [Internet]. Nehren: Hain Lifescience GmbH;2008. [cited 2020 Jul 14]. https://www.hain-lifescience.de/include_datei/kundenmodule/packungsbeilage/download.php?id=936.
22. Ling DI, Zwerling AA, Pai M. GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur Respir J. 2008; 32:1165–74.
Article
23. Theron G, Peter J, Richardson M, Barnard M, Donegan S, Warren R, et al. The diagnostic accuracy of the GenoType(®) MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs. Cochrane Database Syst Rev. 2014; (10):CD010705.
24. World Health Organization. Molecular assays intended as initial tests for the diagnosis of pulmonary and extrapulmonary TB and rifampicin resistance in adults and children: rapid communication [Internet]. Geneva: World Health Organization;2020. [cited 2020 Jun 5]. https://apps.who.int/iris/handle/10665/330395.
25. El-Hajj HH, Marras SA, Tyagi S, Kramer FR, Alland D. Detection of rifampin resistance in Mycobacterium tuberculosis in a single tube with molecular beacons. J Clin Microbiol. 2001; 39:4131–7.
Article
26. Denkinger CM, Schumacher SG, Boehme CC, Dendukuri N, Pai M, Steingart KR. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2014; 44:435–46.
Article
27. Dorman SE, Schumacher SG, Alland D, Nabeta P, Armstrong DT, King B, et al. Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis. 2018; 18:76–84.
28. Feliciano CS, Namburete EI, Rodrigues Plaça J, Peronni K, Dippenaar A, Warren RM, et al. Accuracy of whole genome sequencing versus phenotypic (MGIT) and commercial molecular tests for detection of drug-resistant Mycobacterium tuberculosis isolated from patients in Brazil and Mozambique. Tuberculosis (Edinb). 2018; 110:59–67.
Article
29. Witney AA, Cosgrove CA, Arnold A, Hinds J, Stoker NG, Butcher PD. Clinical use of whole genome sequencing for Mycobacterium tuberculosis. BMC Med. 2016; 14:46.
Article
30. CRyPTIC Consortium and the 100,000 Genomes Project, Allix-Béguec C, Arandjelovic I, Bi L, Beckert P, Bonnet M, et al. Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing. N Engl J Med. 2018; 379:1403–15.
Article
31. Katale BZ, Mbelele PM, Lema NA, Campino S, Mshana SE, Rweyemamu MM, et al. Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania. BMC Genomics. 2020; 21:174.
Article
32. World Health Organization. The use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide [Internet]. Geneva: World Health Organization;2018. [cited 2020 Jul 14]. https://apps.who.int/iris/handle/10665/274443.
33. World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis-2011 update [Internet]. Geneva: World Health Organization;2011. [cited 2020 Jul 14]. https://apps.who.int/iris/bitstream/handle/10665/44597/9789241501583_eng.pdf?sequence=1.
34. World Health Organization. Rapid communication: key changes to treatment of multidrug‐ and rifampicin‐resistant tuberculosis (MDR/RR‐TB) [Internet]. Geneva: World Health Organization;2011. [cited 2020 Jul 14]. https://www.who.int/tb/publications/2018/rapid_communications_MDR/en/.
35. Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment–2017, Ahmad N, Ahuja SD, Akkerman OW, Alffenaar JC, Anderson LF, et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet. 2018; 392:821–34.
36. Bastos ML, Lan Z, Menzies D. An updated systematic review and meta-analysis for treatment of multidrug-resistant tuberculosis. Eur Respir J. 2017; 49:1600803.
Article
37. Joint Committee for the Revision of Korean Guidelines for Tuberculosis; Korean Centers for Disease Control and Prevention. Korean guidelines for tuberculosis. 4th ed. Cheongju: Korea Centers for Disease Control and Prevention;2020.
38. Moadebi S, Harder CK, Fitzgerald MJ, Elwood KR, Marra F. Fluoroquinolones for the treatment of pulmonary tuberculosis. Drugs. 2007; 67:2077–99.
Article
39. Sirgel FA, Warren RM, Streicher EM, Victor TC, van Helden PD, Böttger EC. gyrA mutations and phenotypic susceptibility levels to ofloxacin and moxifloxacin in clinical isolates of Mycobacterium tuberculosis. J Antimicrob Chemother. 2012; 67:1088–93.
Article
40. Migliori GB, Langendam MW, D’Ambrosio L, Centis R, Blasi F, Huitric E, et al. Protecting the tuberculosis drug pipeline: stating the case for the rational use of fluoroquinolones. Eur Respir J. 2012; 40:814–22.
Article
41. Kang YA, Shim TS, Koh WJ, Lee SH, Lee CH, Choi JC, et al. Choice between levofloxacin and moxifloxacin and multidrug-resistant tuberculosis treatment outcomes. Ann Am Thorac Soc. 2016; 13:364–70.
Article
42. Nahid P, Mase SR, Migliori GB, Sotgiu G, Bothamley GH, Brozek JL, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med. 2019; 200:e93–142.
43. Livermore DM. Linezolid in vitro: mechanism and antibacterial spectrum. J Antimicrob Chemother. 2013; 51(Suppl 2):ii9–16.
Article
44. Lan Z, Ahmad N, Baghaei P, Barkane L, Benedetti A, Brode SK, et al. Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet Respir Med. 2020; 8:383–94.
Article
45. Koh WJ, Kang YR, Jeon K, Kwon OJ, Lyu J, Kim WS, et al. Daily 300 mg dose of linezolid for multidrug-resistant and extensively drug-resistant tuberculosis: updated analysis of 51 patients. J Antimicrob Chemother. 2012; 67:1503–7.
Article
46. Sotgiu G, Centis R, D’Ambrosio L, Alffenaar JW, Anger HA, Caminero JA, et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012; 40:1430–42.
Article
47. Koul A, Dendouga N, Vergauwen K, Molenberghs B, Vranckx L, Willebrords R, et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat Chem Biol. 2007; 3:323–4.
Article
48. 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; 56:1444–51.
Article
49. 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; 371:723–32.
Article
50. 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; 360:2397–405.
Article
51. Centers for Disease Control and Prevention. Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (Sirturo) for the treatment of multidrug-resistant tuberculosis. MMWR Recomm Rep. 2013; 62(RR-09):1–12.
52. 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:e466.
Article
53. Barry PJ, O’Connor TM. Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007; 14:2000–8.
Article
54. Kim CT, Kim TO, Shin HJ, Ko YC, Choe YH, Kim HR, et al. Bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis: a multicentre cohort study in Korea. Eur Respir J. 2018; 51:1702467.
Article
55. Mok J, Kang H, Koh WJ, Jhun BW, Yim JJ, Kwak N, et al. Final treatment outcomes of delamanid-containing regimens in patients with MDR-/XDR-TB in South Korea. Eur Respir J. 2019; 54:1900811.
Article
56. Ferlazzo G, Mohr E, Laxmeshwar C, Hewison C, Hughes J, Jonckheere S, et al. Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug-resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study. Lancet Infect Dis. 2018; 18:536–44.
Article
57. Lange C, Duarte R, Fréchet-Jachym M, Guenther G, Guglielmetti L, Olaru ID, et al. Limited benefit of the new shorter multidrug-resistant tuberculosis regimen in Europe. Am J Respir Crit Care Med. 2016; 194:1029–31.
Article
58. Cegielski JP, Kurbatova E, van der Walt M, Brand J, Ershova J, Tupasi T, et al. Multidrug-resistant tuberculosis treatment outcomes in relation to treatment and initial versus acquired second-line drug resistance. Clin Infect Dis. 2016; 62:418–30.
Article
59. 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; 182:684–92.
Article
60. Nunn AJ, Phillips PP, Meredith SK, Chiang CY, Conradie F, Dalai D, et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med. 2019; 380:1201–13.
Article
Full Text Links
  • YUJM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr