Tuberc Respir Dis.  2020 Jan;83(1):20-30. 10.4046/trd.2019.0065.

Treatment of Isoniazid-Resistant Pulmonary Tuberculosis

Affiliations
  • 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wjkoh@skku.edu

Abstract

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only first-line drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

Keyword

Tuberculosis; Isoniazid; Resistance; Treatment

MeSH Terms

Cause of Death
Diagnosis
Humans
Isoniazid
Public Health
Rifampin
Tuberculosis
Tuberculosis, Pulmonary*
World Health Organization
Isoniazid
Rifampin

Reference

1. World Health Organization. Global tuberculosis report 2018 [Internet]. Geneva: World Health Organization;2018. cited 2018 Dec 18. Available from: https://www.who.int/tb/publications/global_report/en/.
2. Cho KS. Tuberculosis control in the Republic of Korea. Epidemiol Health. 2018; 40:e2018036. PMID: 30081621.
Article
3. Kim JH, Yim JJ. Achievements in and challenges of tuberculosis control in South Korea. Emerg Infect Dis. 2015; 21:1913–1920. PMID: 26485188.
Article
4. Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015; 372:2127–2135. PMID: 26017823.
5. Pai M, Behr MA, Dowdy D, Dheda K, Divangahi M, Boehme CC, et al. Tuberculosis. Nat Rev Dis Primers. 2016; 2:16076. PMID: 27784885.
Article
6. Lee SH. Tuberculosis infection and latent tuberculosis. Tuberc Respir Dis. 2016; 79:201–206.
Article
7. Hoopes AJ, Kammerer JS, Harrington TA, Ijaz K, Armstrong LR. Isoniazid-monoresistant tuberculosis in the United States, 1993 to 2003. Arch Intern Med. 2008; 168:1984–1992. PMID: 18852399.
Article
8. Jenkins HE, Zignol M, Cohen T. Quantifying the burden and trends of isoniazid resistant tuberculosis, 1994-2009. PLoS One. 2011; 6:e22927. PMID: 21829557.
Article
9. Kim SJ, Bai GH, Hong YP. Drug-resistant tuberculosis in Korea, 1994. Int J Tuberc Lung Dis. 1997; 1:302–308. PMID: 9432384.
10. Kim SJ, Hong YP. Drug resistance of Mycobacterium tuberculosis in Korea. Tuber Lung Dis. 1992; 73:219–224. PMID: 1477389.
11. Hong YP, Kim SJ, Kwon DW, Chang SC, Lew WJ, Han YC. The sixth Nationwide Tuberculosis Prevalence Survey in Korea, 1990. Tuber Lung Dis. 1993; 74:323–331. PMID: 8292205.
Article
12. Bai GH, Park YK, Choi YW, Bai JI, Kim HJ, Chang CL, et al. Trend of anti-tuberculosis drug resistance in Korea, 1994–2004. Int J Tuberc Lung Dis. 2007; 11:571–576. PMID: 17439684.
13. Kim J, Park YJ, Lee NY, Chang CL, Lee M, Shin JH. Anti-tuberculosis drug resistant rates in Mycobacterium tuberculosis Isolated from respiratory specimens: a multicenter study in Korea. Ann Clin Microbiol. 2013; 16:1–7.
14. Kim H, Mok JH, Kang B, Lee T, Lee HK, Jang HJ, et al. Trend of multidrug and fluoroquinolone resistance in Mycobacterium tuberculosis isolates from 2010 to 2014 in Korea: a multicenter study. Korean J Intern Med. 2019; 34:344–352. PMID: 30045614.
15. Mahmoudi A, Iseman MD. Pitfalls in the care of patients with tuberculosis: common errors and their association with the acquisition of drug resistance. JAMA. 1993; 270:65–68. PMID: 8510299.
Article
16. Espinal MA, Kim SJ, Suarez PG, Kam KM, Khomenko AG, Migliori GB, et al. Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries. JAMA. 2000; 283:2537–2545. PMID: 10815117.
17. Menzies D, Benedetti A, Paydar A, Martin I, Royce S, Pai M, et al. Effect of duration and intermittency of rifampin on tuberculosis treatment outcomes: a systematic review and meta-analysis. PLoS Med. 2009; 6:e1000146. PMID: 19753109.
Article
18. Menzies D, Benedetti A, Paydar A, Royce S, Madhukar P, Burman W, et al. Standardized treatment of active tuberculosis in patients with previous treatment and/or with mono-resistance to isoniazid: a systematic review and meta-analysis. PLoS Med. 2009; 6:e1000150. PMID: 20101802.
Article
19. Mitchison DA, Nunn AJ. Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis. 1986; 133:423–430. PMID: 2420242.
20. Hong Kong Chest Service/British Medical Research Council. Five-year follow-up of a controlled trial of five 6-month regimens of chemotherapy for pulmonary tuberculosis. Am Rev Respir Dis. 1987; 136:1339–1342. PMID: 2891333.
21. Gegia M, Cohen T, Kalandadze I, Vashakidze L, Furin J. Outcomes among tuberculosis patients with isoniazid resistance in Georgia, 2007–2009. Int J Tuberc Lung Dis. 2012; 16:812–816. PMID: 22507372.
Article
22. Gegia M, Winters N, Benedetti A, van Soolingen D, Menzies D. Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis. Lancet Infect Dis. 2017; 17:223–234. PMID: 27865891.
Article
23. Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003; 167:603–662. PMID: 12588714.
24. World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drugresistant tuberculosis [Internet]. Geneva: World Health Organization;2014. cited 2019 Jun 1. Available from: https://www.who.int/tb/publications/pmdt_companionhandbook/en/.
25. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children [Internet]. Geneva: World Health Organization;2006. cited 2019 Jun 1. Available from: https://www.who.int/maternal_child_adolescent/documents/htm_tb_2006_371/en/.
26. World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis (emergency update 2008) [Internet]. Geneva: World Health Organization;2008. cited 2019 Jun 1. Available from: https://apps.who.int/iris/handle/10665/43965.
27. Escalante P, Graviss EA, Griffith DE, Musser JM, Awe RJ. Treatment of isoniazid-resistant tuberculosis in southeastern Texas. Chest. 2001; 119:1730–1736. PMID: 11399698.
Article
28. Kim YH, Suh GY, Chung MP, Kim H, Kwon OJ, Lim SY, et al. Treatment of isoniazid-resistant pulmonary tuberculosis. BMC Infect Dis. 2008; 8:6. PMID: 18211720.
Article
29. Cattamanchi A, Dantes RB, Metcalfe JZ, Jarlsberg LG, Grinsdale J, Kawamura LM, et al. Clinical characteristics and treatment outcomes of patients with isoniazid-monoresistant tuberculosis. Clin Infect Dis. 2009; 48:179–185. PMID: 19086909.
Article
30. Bang D, Andersen PH, Andersen AB, Thomsen VO. Isoniazid-resistant tuberculosis in Denmark: mutations, transmission and treatment outcome. J Infect. 2010; 60:452–457. PMID: 20347869.
Article
31. Munang ML, Kariuki M, Dedicoat M. Isoniazid-resistant tuberculosis in Birmingham, United Kingdom, 1999-2010. QJM. 2015; 108:19–25. PMID: 24989780.
Article
32. Romanowski K, Chiang LY, Roth DZ, Krajden M, Tang P, Cook VJ, et al. Treatment outcomes for isoniazid-resistant tuberculosis under program conditions in British Columbia, Canada. BMC Infect Dis. 2017; 17:604. PMID: 28870175.
Article
33. Stagg HR, Harris RJ, Hatherell HA, Obach D, Zhao H, Tsuchiya N, et al. What are the most efficacious treatment regimens for isoniazid-resistant tuberculosis? A systematic review and network meta-analysis. Thorax. 2016; 71:940–949. PMID: 27298314.
Article
34. Stagg HR, Lipman MC, McHugh TD, Jenkins HE. Isoniazid-resistant tuberculosis: a cause for concern? Int J Tuberc Lung Dis. 2017; 21:129–139. PMID: 28234075.
Article
35. Stagg HR, Bothamley GH, Davidson JA, Kunst H, Lalor MK, Lipman MC, et al. Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance. Eur Respir J. 2019; 54:1900982. PMID: 31371444.
Article
36. Fregonese F, Ahuja SD, Akkerman OW, Arakaki-Sanchez D, Ayakaka I, Baghaei P, et al. Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis. Lancet Respir Med. 2018; 6:265–275. PMID: 29595509.
Article
37. World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment [Internet]. Geneva: World Health Organization;2019. cited 2019 Jun 1. Available from: https://www.who.int/tb/publications/2019/consolidated-guidelines-drug-resistant-TB-treatment/en/.
38. Stewart SM, Crofton JW. The clinical significance of low degrees of drug resistance in pulmonary tuberculosis. Am Rev Respir Dis. 1964; 89:811–829. PMID: 14169411.
39. World Health Organization. WHO treatment guidelines for isoniazid-resistant tuberculosis: supplement to the WHO treatment guidelines for drug-resistant tuberculosis [Internet]. Geneva: World Health Organization;2018. cited 2019 Jun 1. Available from: https://www.who.int/tb/publications/2018/WHO_guidelines_isoniazid_resistant_TB/en/.
40. Zhang Y, Heym B, Allen B, Young D, Cole S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature. 1992; 358:591–593. PMID: 1501713.
41. Piatek AS, Telenti A, Murray MR, El-Hajj H, Jacobs WR Jr, Kramer FR, et al. Genotypic analysis of Mycobacterium tuberculosis in two distinct populations using molecular beacons: implications for rapid susceptibility testing. Antimicrob Agents Chemother. 2000; 44:103–110. PMID: 10602730.
42. Ramaswamy SV, Reich R, Dou SJ, Jasperse L, Pan X, Wanger A, et al. Single nucleotide polymorphisms in genes associated with isoniazid resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2003; 47:1241–1250. PMID: 12654653.
43. Ramaswamy S, Musser JM. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber Lung Dis. 1998; 79:3–29. PMID: 10645439.
44. Dalla Costa ER, Ribeiro MO, Silva MS, Arnold LS, Rostirolla DC, Cafrune PI, et al. Correlations of mutations in katG, oxyRahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America. BMC Microbiol. 2009; 9:39. PMID: 19228426.
Article
45. Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science. 1994; 263:227–230. PMID: 8284673.
46. Canetti G. Present aspects of bacterial resistance in tuberculosis. Am Rev Respir Dis. 1965; 92:687–703. PMID: 5321145.
47. Mitchison DA. How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. Int J Tuberc Lung Dis. 1998; 2:10–15. PMID: 9562106.
48. Patel KB, Belmonte R, Crowe HM. Drug malabsorption and resistant tuberculosis in HIV-infected patients. N Engl J Med. 1995; 332:336–337.
Article
49. Moore M, Onorato IM, McCray E, Castro KG. Trends in drugresistant tuberculosis in the United States, 1993–1996. JAMA. 1997; 278:833–837. PMID: 9293991.
Article
50. Forssbohm M, Loddenkemper R, Rieder HL. Isoniazid resistance among tuberculosis patients by birth cohort in Germany. Int J Tuberc Lung Dis. 2003; 7:973–979. PMID: 14552568.
51. Fox L, Kramer MR, Haim I, Priess R, Metvachuk A, Shitrit D. Comparison of isoniazid monoresistant tuberculosis with drug-susceptible tuberculosis and multidrug-resistant tuberculosis. Eur J Clin Microbiol Infect Dis. 2011; 30:863–867. PMID: 21431989.
Article
52. Bass JB Jr, Farer LS, Hopewell PC, O’Brien R, Jacobs RF, Ruben F, et al. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J Respir Crit Care Med. 1994; 149:1359–1374. PMID: 8173779.
Article
53. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax. 1998; 53:536–548. PMID: 9797751.
54. National Collaborating Centre for Chronic Conditions. Centre for Clinical Practice at NICE. Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control. London: National Institute for Health and Clinical Excellence;2011.
55. National Institute for Health and Care Excellence. Tuberculosis: NICE guideline (NG33) [Internet]. London: National Institute for Health and Care Excellence;2016. cited 2019 Jun 1. Available from: https://www.nice.org.uk/guidance/ng33.
56. Tam CM, Chan SL, Lam CW, Leung CC, Kam KM, Morris JS, et al. Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Initial report. Am J Respir Crit Care Med. 1998; 157(6 pt 1):1726–1733. PMID: 9620898.
57. Bai KJ, Yu MC, Suo J, Chiang CY, Chiang IH, Lin TP, et al. Short-course chemotherapy for isoniazid-resistant pulmonary tuberculosis. J Formos Med Assoc. 1998; 97:278–282. PMID: 9585680.
58. Babu Swai O, Aluoch JA, Githui WA, Thiong’o R, Edwards EA, Darbyshire JH, et al. Controlled clinical trial of a regimen of two durations for the treatment of isoniazid resistant pulmonary tuberculosis. Tubercle. 1988; 69:5–14. PMID: 3051607.
Article
59. Ormerod LP, Horsfield N, Green RM. Can a nine-month regimen be used to treat isoniazid resistant tuberculosis diagnosed after standard treatment is started? J Infect. 2001; 42:1–3. PMID: 11243745.
Article
60. Nolan CM, Goldberg SV. Treatment of isoniazid-resistant tuberculosis with isoniazid, rifampin, ethambutol, and pyrazinamide for 6 months. Int J Tuberc Lung Dis. 2002; 6:952–958. PMID: 12475140.
61. Tuberculosis Research Centre. A controlled clinical trial of oral short-course regimens in the treatment of sputum-positive pulmonary tuberculosis. Int J Tuberc Lung Dis. 1997; 1:509–517. PMID: 9487448.
62. Seung KJ, Gelmanova IE, Peremitin GG, Golubchikova VT, Pavlova VE, Sirotkina OB, et al. The effect of initial drug resistance on treatment response and acquired drug resistance during standardized short-course chemotherapy for tuberculosis. Clin Infect Dis. 2004; 39:1321–1328. PMID: 15494909.
Article
63. Wang TY, Lin SM, Shie SS, Chou PC, Huang CD, Chung FT, et al. Clinical characteristics and treatment outcomes of patients with low- and high-concentration isoniazid-monoresistant tuberculosis. PLoS One. 2014; 9:e86316. PMID: 24466020.
Article
64. Baez-Saldana R, Delgado-Sanchez G, Garcia-Garcia L, Cruz-Hervert LP, Montesinos-Castillo M, Ferreyra-Reyes L, et al. Isoniazid mono-resistant tuberculosis: impact on treatment outcome and survival of pulmonary tuberculosis patients in Southern Mexico 1995-2010. PLoS One. 2016; 11:e0168955. PMID: 28030600.
Article
65. Deepa D, Achanta S, Jaju J, Rao K, Samyukta R, Claassens M, et al. The impact of isoniazid resistance on the treatment outcomes of smear positive re-treatment tuberculosis patients in the state of Andhra Pradesh, India. PLoS One. 2013; 8:e76189. PMID: 24146839.
Article
66. Koh WJ, Kwon OJ, Park YK, Lew WJ, Bai GH. Development of multidrug resistance during treatment of isoniazid-resistant tuberculosis. Eur Respir J. 2005; 26:557. PMID: 16135740.
Article
67. Low rate of emergence of drug resistance in sputum positive patients treated with short course chemotherapy. Int J Tuberc Lung Dis. 2001; 5:40–45. PMID: 11263515.
68. Jacobson KR, Theron D, Victor TC, Streicher EM, Warren RM, Murray MB. Treatment outcomes of isoniazid-resistant tuberculosis patients, Western Cape Province, South Africa. Clin Infect Dis. 2011; 53:369–372. PMID: 21810750.
Article
69. Lee H, Jeong BH, Park HY, Jeon K, Huh HJ, Lee NY, et al. Treatment outcomes with fluoroquinolone-containing regimens for isoniazid-resistant pulmonary tuberculosis. Antimicrob Agents Chemother. 2016; 60:471–477. PMID: 26525801.
Article
70. Chien JY, Chen YT, Wu SG, Lee JJ, Wang JY, Yu CJ. Treatment outcome of patients with isoniazid mono-resistant tuberculosis. Clin Microbiol Infect. 2015; 21:59–68. PMID: 25636929.
Article
71. Villegas L, Otero L, Sterling TR, Huaman MA, Van der, Gotuzzo E, et al. Prevalence, risk factors, and treatment outcomes of isoniazid- and rifampicin-mono-resistant pulmonary tuberculosis in Lima, Peru. PLoS One. 2016; 11:e0152933. PMID: 27045684.
72. Cornejo Garcia JG, Alarcon Guizado VA, Mendoza Ticona A, Alarcon E, Heldal E, Moore DA. Treatment outcomes for isoniazid-monoresistant tuberculosis in Peru, 2012–2014. PLoS One. 2018; 13:e0206658. PMID: 30513085.
Article
73. Public Health Agency of Canada. Canadian Tuberculosis Standards. 7th Edition. Chapter 8: Drug-resistant tuberculosis [Internet]. Ottawa: Public Health Agency of Canada;2014. cited 2019 Jun 1. Available from: https://www.canada.ca/en/public-health/services/infectious-diseases/canadian-tuberculosis-standards-7th-edition.html.
74. 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; 180:273–280. PMID: 19406981.
Article
75. Ramachandran G, Hemanth Kumar AK, Srinivasan R, Geetharani A, Sugirda P, Nandhakumar B, et al. Effect of rifampicin & isoniazid on the steady state pharmacokinetics of moxifloxacin. Indian J Med Res. 2012; 136:979–984. PMID: 23391793.
76. Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997; 32:101–119. PMID: 9068926.
Article
77. Centers for Disease Control and Prevention (CDC). Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations: United States, 2001. MMWR Morb Mortal Wkly Rep. 2001; 50:733–735. PMID: 11787580.
78. Lempens P, Meehan CJ, Vandelannoote K, Fissette K, de Rijk P, Van Deun A, et al. Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations. Sci Rep. 2018; 8:3246. PMID: 29459669.
Article
Full Text Links
  • TRD
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