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Treatment of Mycobacterium avium Complex Pulmonary Disease

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2019, v.82 no.1, pp.15-26


Charles L. Daley (National Jewish Health)
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Abstract

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

keywords
Nontuberculous Mycobacteria, Mycobacterium avium Complex, Mycobacterium avium, Mycobacterium intracellulare, Treatment

Reference

1.

1. Falkinham JO 3rd. Environmental sources of nontuberculous mycobacteria. Clin Chest Med 2015; 36:35-41.

2.

2. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175:367-416.

3.

3. Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax 2017; 72:ii1-64.

4.

4. Daley CL. Mycobacterium avium complex disease. Microbiol Spectr 2017;5:TNMI7-0045-2017.

5.

5. Koh WJ. Nontuberculous mycobacteria: overview. Microbiol Spectr 2017;5:TNMI7-0024-2016.

6.

6. Ryu YJ, Koh WJ, Daley CL. Diagnosis and treatment of nontuberculous mycobacterial lung disease: clinicians’ perspectives. Tuberc Respir Dis 2016; 79:74-84.

7.

7. Kwon YS, Koh WJ. Diagnosis and treatment of nontuberculous mycobacterial lung disease. J Korean Med Sci 2016; 31:649-59.

8.

8. Hoefsloot W, van Ingen J, Andrejak C, Angeby K, Bauriaud R, Bemer P, et al. The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTMNET collaborative study. Eur Respir J 2013; 42:1604-13.

9.

9. Moon SM, Kim SY, Jhun BW, Lee H, Park HY, Jeon K, et al. Clinical characteristics and treatment outcomes of pulmonary disease caused by Mycobacterium chimaera . Diagn Microbiol Infect Dis 2016; 86:382-4.

10.

10. Kim SY, Shin SH, Moon SM, Yang B, Kim H, Kwon OJ, et al. Distribution and clinical significance of Mycobacterium avium complex species isolated from respiratory specimens. Diagn Microbiol Infect Dis 2017; 88:125-37.

11.

11. Schweickert B, Goldenberg O, Richter E, Gobel UB, Petrich A, Buchholz P, et al. Occurrence and clinical relevance of Mycobacterium chimaera sp. nov., Germany. Emerg Infect Dis 2008; 14:1443-6.

12.

12. Boyle DP, Zembower TR, Reddy S, Qi C. Comparison of clinical features, virulence, and relapse among Mycobacterium avium complex species. Am J Respir Crit Care Med 2015; 191:1310-7.

13.

13. Kitada S, Uenami T, Yoshimura K, Tateishi Y, Miki K, Miki M, et al. Long-term radiographic outcome of nodular bronchiectatic Mycobacterium avium complex pulmonary disease. Int J Tuberc Lung Dis 2012; 16:660-4.

14.

14. Hayashi M, Takayanagi N, Kanauchi T, Miyahara Y, Yanagisawa T, Sugita Y. Prognostic factors of 634 HIV-negative patients with Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2012; 185:575-83.

15.

15. Lee G, Lee KS, Moon JW, Koh WJ, Jeong BH, Jeong YJ, et al. Nodular bronchiectatic Mycobacterium avium complex pulmonary disease: natural course on serial computed tomographic scans. Ann Am Thorac Soc 2013; 10:299-306.

16.

16. Gochi M, Takayanagi N, Kanauchi T, Ishiguro T, Yanagisawa T, Sugita Y. Retrospective study of the predictors of mortality and radiographic deterioration in 782 patients with nodular/bronchiectatic Mycobacterium avium complex lung disease. BMJ Open 2015; 5:e008058.

17.

17. Koh WJ, Moon SM, Kim SY, Woo MA, Kim S, Jhun BW, et al. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype. Eur Respir J 2017; 50:1602503.

18.

18. Kendall BA, Winthrop KL. Update on the epidemiology of pulmonary nontuberculous mycobacterial infections. Semin Respir Crit Care Med 2013; 34:87-94.

19.

19. Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med 2015; 36:13-34.

20.

20. Ko RE, Moon SM, Ahn S, Jhun BW, Jeon K, Kwon OJ, et al. Changing epidemiology of nontuberculous mycobacterial lung diseases in a tertiary referral hospital in Korea between 2001 and 2015. J Korean Med Sci 2018; 33:e65.

21.

21. Koh WJ, Kwon OJ, Jeon K, Kim TS, Lee KS, Park YK, et al. Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea. Chest 2006; 129:341-8.

22.

22. Park YS, Lee CH, Lee SM, Yang SC, Yoo CG, Kim YW, et al. Rapid increase of non-tuberculous mycobacterial lung diseases at a tertiary referral hospital in South Korea. Int J Tuberc Lung Dis 2010; 14:1069-71.

23.

23. Lee SK, Lee EJ, Kim SK, Chang J, Jeong SH, Kang YA. Changing epidemiology of nontuberculous mycobacterial lung disease in South Korea. Scand J Infect Dis 2012; 44:733-8.

24.

24. Yoo JW, Jo KW, Kim MN, Lee SD, Kim WS, Kim DS, et al. Increasing trend of isolation of non-tuberculous mycobacteria in a tertiary university hospital in South Korea. Tuberc Respir Dis 2012; 72:409-15.

25.

25. Koh WJ, Jeong BH, Jeon K, Lee NY, Lee KS, Woo SY, et al. Clinical significance of the differentiation between Mycobacterium avium and Mycobacterium intracellulare in M avium complex lung disease. Chest 2012; 142:1482-8.

26.

26. Hwang JA, Kim S, Jo KW, Shim TS. Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course. Eur Respir J 2017; 49:1600537.

27.

27. Pan SW, Shu CC, Feng JY, Wang JY, Chan YJ, Yu CJ, et al. Microbiological persistence in patients with Mycobacterium avium complex lung disease: the predictors and the Impact on radiographic progression. Clin Infect Dis 2017; 65:927-34.

28.

28. Henkle E, Novosad SA, Shafer S, Hedberg K, Siegel SAR, Ku J, et al. Long-term outcomes in a population-based cohort with respiratory nontuberculous mycobacteria isolation. Ann Am Thorac Soc 2017; 14:1120-8.

29.

29. Kim SJ, Park J, Lee H, Lee YJ, Park JS, Cho YJ, et al. Risk factors for deterioration of nodular bronchiectatic Mycobacterium avium complex lung disease. Int J Tuberc Lung Dis 2014; 18:730-6.

30.

30. Kim SJ, Yoon SH, Choi SM, Lee J, Lee CH, Han SK, et al. Characteristics associated with progression in patients with of nontuberculous mycobacterial lung disease : a prospective cohort study. BMC Pulm Med 2017; 17:5.

31.

31. Wallace RJ Jr, Brown-Elliott BA, McNulty S, Philley JV, Killingley J, Wilson RW, et al. Macrolide/Azalide therapy for nodular/bronchiectatic Mycobacterium avium complex lung disease. Chest 2014; 146:276-82.

32.

32. Jeong BH, Jeon K, Park HY, Kim SY, Lee KS, Huh HJ, et al. Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2015; 191:96-103.

33.

33. Adjemian J, Prevots DR, Gallagher J, Heap K, Gupta R, Griffith D. Lack of adherence to evidence-based treatment guidelines for nontuberculous mycobacterial lung disease. Ann Am Thorac Soc 2014; 11:9-16.

34.

34. van Ingen J, Wagner D, Gallagher J, Morimoto K, Lange C, Haworth CS, et al. Poor adherence to management guidelines in nontuberculous mycobacterial pulmonary diseases. Eur Respir J 2017; 49:1601855.

35.

35. Field SK, Fisher D, Cowie RL. Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest 2004; 126:566-81.

36.

36. Xu HB, Jiang RH, Li L. Treatment outcomes for Mycobacterium avium complex: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 2014; 33:347-58.

37.

37. Kwak N, Park J, Kim E, Lee CH, Han SK, Yim JJ. Treatment outcomes of Mycobacterium avium complex lung disease:a systematic review and meta-analysis. Clin Infect Dis 2017; 65:1077-84.

38.

38. Pasipanodya JG, Ogbonna D, Deshpande D, Srivastava S, Gumbo T. Meta-analyses and the evidence base for microbial outcomes in the treatment of pulmonary Mycobacterium avium-intracellulare complex disease. J Antimicrob Chemother 2017; 72(Suppl_2):i3-19.

39.

39. Diel R, Nienhaus A, Ringshausen FC, Richter E, Welte T, Rabe KF, et al. Microbiologic outcome of interventions against Mycobacterium avium complex pulmonary disease: a systematic review. Chest 2018; 153:888-921.

40.

40. Griffith DE, Adjemian J, Brown-Elliott BA, Philley JV, Prevots DR, Gaston C, et al. Semiquantitative culture analysis during therapy for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2015; 192:754-60.

41.

41. Loebinger MR. Mycobacterium avium complex infection:phenotypes and outcomes. Eur Respir J 2017; 50:1701380.

42.

42. Griffith DE, Brown-Elliott BA, Shepherd S, McLarty J, Griffith L, Wallace RJ Jr. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2005; 172:250-3.

43.

43. Lam PK, Griffith DE, Aksamit TR, Ruoss SJ, Garay SM, Daley CL, et al. Factors related to response to intermittent treatment of Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2006; 173:1283-9.

44.

44. Jeong BH, Jeon K, Park HY, Moon SM, Kim SY, Lee SY, et al. Peak plasma concentration of azithromycin and treatment responses in Mycobacterium avium complex lung disease. Antimicrob Agents Chemother 2016; 60:6076-83.

45.

45. Philley JV, Griffith DE. Treatment of slowly growing mycobacteria. Clin Chest Med 2015; 36:79-90.

46.

46. Jhun BW, Kim SY, Moon SM, Jeon K, Kwon OJ, Huh HJ, et al. Development of macrolide resistance and reinfection in refractory Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2018; 198:1322-30.

47.

47. Wallace RJ Jr, Brown BA, Griffith DE, Girard WM, Murphy DT, Onyi GO, et al. Initial clarithromycin monotherapy for Mycobacterium avium-intracellulare complex lung disease. Am J Respir Crit Care Med 1994; 149:1335-41.

48.

48. Griffith DE, Brown BA, Girard WM, Murphy DT, Wallace RJ Jr. Azithromycin activity against Mycobacterium avium complex lung disease in patients who were not infected with human immunodeficiency virus. Clin Infect Dis 1996; 23:983-9.

49.

49. Wallace RJ Jr, Brown BA, Griffith DE, Girard WM, Murphy DT. Clarithromycin regimens for pulmonary Mycobacterium avium complex. The first 50 patients. Am J Respir Crit Care Med 1996; 153(6 Pt 1):1766-72.

50.

50. Griffith DE, Brown BA, Murphy DT, Girard WM, Couch L, Wallace RJ Jr. Initial (6-month) results of three-times-weekly azithromycin in treatment regimens for Mycobacterium avium complex lung disease in human immunodeficiency virus-negative patients. J Infect Dis 1998; 178:121-6.

51.

51. Jhun BW, Moon SM, Kim SY, Park HY, Jeon K, Kwon OJ, et al. Intermittent antibiotic therapy for recurrent nodular bronchiectatic Mycobacterium avium complex lung disease. Antimicrob Agents Chemother 2018:e01812-17.

52.

52. Griffith DE, Brown-Elliott BA, Langsjoen B, Zhang Y, Pan X, Girard W, et al. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2006; 174:928-34.

53.

53. Kadota T, Matsui H, Hirose T, Suzuki J, Saito M, Akaba T, et al. Analysis of drug treatment outcome in clarithromycinresistant Mycobacterium avium complex lung disease. BMC Infect Dis 2016; 16:31.

54.

54. Moon SM, Park HY, Kim SY, Jhun BW, Lee H, Jeon K, et al. Clinical characteristics, treatment outcomes, and resistance mutations associated with macrolide-resistant Mycobacterium avium complex lung disease. Antimicrob Agents Chemother 2016; 60:6758-65.

55.

55. Morimoto K, Namkoong H, Hasegawa N, Nakagawa T, Morino E, Shiraishi Y, et al. Macrolide-resistant Mycobacterium avium complex lung disease: analysis of 102 consecutive cases. Ann Am Thorac Soc 2016; 13:1904-11.

56.

56. Koh WJ, Hong G, Kim SY, Jeong BH, Park HY, Jeon K, et al. Treatment of refractory Mycobacterium avium complex lung disease with a moxifloxacin-containing regimen. Antimicrob Agents Chemother 2013; 57:2281-5.

57.

57. Kang HK, Park HY, Kim D, Jeong BH, Jeon K, Cho JH, et al. Treatment outcomes of adjuvant resectional surgery for nontuberculous mycobacterial lung disease. BMC Infect Dis 2015; 15:76.

58.

58. Asakura T, Hayakawa N, Hasegawa N, Namkoong H, Takeuchi K, Suzuki S, et al. Long-term outcome of pulmonary resection for nontuberculous mycobacterial pulmonary disease. Clin Infect Dis 2017; 65:244-51.

59.

59. Mitchell JD, Bishop A, Cafaro A, Weyant MJ, Pomerantz M. Anatomic lung resection for nontuberculous mycobacterial disease. Ann Thorac Surg 2008; 85:1887-92.

60.

60. Mitchell JD. Surgical approach to pulmonary nontuberculous mycobacterial infections. Clin Chest Med 2015; 36:117-22.

61.

61. 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; 60:1361-7.

62.

62. Field SK, Cowie RL. Treatment of Mycobacterium aviumintracellulare complex lung disease with a macrolide, ethambutol, and clofazimine. Chest 2003; 124:1482-6.

63.

63. Jarand J, Davis JP, Cowie RL, Field SK, Fisher DA. Long-term follow-up of Mycobacterium avium complex lung disease in patients treated with regimens including clofazimine and/or rifampin. Chest 2016; 149:1285-93.

64.

64. Martiniano SL, Wagner BD, Levin A, Nick JA, Sagel SD, Daley CL. Safety and effectiveness of clofazimine for primary and refractory nontuberculous mycobacterial infection. Chest 2017; 152:800-9.

65.

65. Olivier KN, Shaw PA, Glaser TS, Bhattacharyya D, Fleshner M, Brewer CC, et al. Inhaled amikacin for treatment of refractory pulmonary nontuberculous mycobacterial disease. Ann Am Thorac Soc 2014; 11:30-5.

66.

66. Yagi K, Ishii M, Namkoong H, Asami T, Iketani O, Asakura T, et al. The efficacy, safety, and feasibility of inhaled amikacin for the treatment of difficult-to-treat non-tuberculous mycobacterial lung diseases. BMC Infect Dis 2017; 17:558.

67.

67. Jhun BW, Yang B, Moon SM, Lee H, Park HY, Jeon K, et al. Amikacin inhalation as salvage therapy for refractory nontuberculous mycobacterial lung disease. Antimicrob Agents Chemother 2018:e00011-18.

68.

68. Rose SJ, Neville ME, Gupta R, Bermudez LE. Delivery of aerosolized liposomal amikacin as a novel approach for the treatment of nontuberculous mycobacteria in an experimental model of pulmonary infection. PLoS One 2014; 9:e108703.

69.

69. Olivier KN, Griffith DE, Eagle G, McGinnis JP 2nd, Micioni L, Liu K, et al. Randomized trial of liposomal amikacin for inhalation in nontuberculous mycobacterial lung disease. Am J Respir Crit Care Med 2017; 195:814-23.

70.

70. Griffith DE, Eagle G, Thomson R, Aksamit TR, Hasegawa N, Morimoto K, et al. Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT): a prospective, open-label, randomized study. Am J Respir Crit Care Med 2018 Sep 14[Epub]. https://doi.org/10.1164/rccm.201807-1318OC.

71.

71. Kwon YS, Jeong BH, Koh WJ. Tuberculosis: clinical trials and new drug regimens. Curr Opin Pulm Med 2014; 20:280-6.

72.

72. Kwon YS, Koh WJ. Synthetic investigational new drugs for the treatment of tuberculosis. Expert Opin Investig Drugs 2016; 25:183-93.

73.

73. Brown-Elliott BA, Philley JV, Griffith DE, Thakkar F, Wallace RJ Jr. In vitro susceptibility testing of bedaquiline against Mycobacterium avium complex. Antimicrob Agents Chemother 2017; 61:e01798-16.

74.

74. Vesenbeckh S, Schonfeld N, Krieger D, Bettermann G, Bauer TT, Russmann H, et al. Bedaquiline as a potential agent in the treatment of M. intracellulare and M. avium infections. Eur Respir J 2017; 49:1601969.

75.

75. Philley JV, Wallace RJ Jr, Benwill JL, Taskar V, Brown-Elliott BA, Thakkar F, et al. Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease. Chest 2015; 148:499-506.

76.

76. van Ingen J, Aksamit T, Andrejak C, Bottger EC, Cambau E, Daley CL, et al. Treatment outcome definitions in nontuberculous mycobacterial pulmonary disease: an NTM-NET consensus statement. Eur Respir J 2018; 51:1800170.

77.

77. Satta G, McHugh TD, Mountford J, Abubakar I, Lipman M. Managing pulmonary nontuberculous mycobacterial infection. time for a patient-centered approach. Ann Am Thorac Soc 2014; 11:117-21.

78.

78. Mehta M, Marras TK. Impaired health-related quality of life in pulmonary nontuberculous mycobacterial disease. Respir Med 2011; 105:1718-25.

79.

79. Lee MR, Yang CY, Chang KP, Keng LT, Yen DH, Wang JY, et al. Factors associated with lung function decline in patients with non-tuberculous mycobacterial pulmonary disease. PLoS One 2013; 8:e58214.

80.

80. Park HY, Jeong BH, Chon HR, Jeon K, Daley CL, Koh WJ. Lung function decline according to clinical course in nontuberculous mycobacterial lung disease. Chest 2016; 150:1222-32.

81.

81. Asakura T, Funatsu Y, Ishii M, Namkoong H, Yagi K, Suzuki S, et al. Health-related quality of life is inversely correlated with C-reactive protein and age in Mycobacterium avium complex lung disease: a cross-sectional analysis of 235 patients. Respir Res 2015; 16:145.

82.

82. Hama M, Ushiki A, Kosaka M, Yamazaki Y, Yasuo M, Yamamoto H, et al. Health-related quality of life in patients with pulmonary non-tuberculous mycobacteria infection. Int J Tuberc Lung Dis 2016; 20:747-52.

83.

83. Asakura T, Ishii M, Ishii K, Suzuki S, Namkoong H, Okamori S, et al. Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital. Int J Tuberc Lung Dis 2018; 22:695-703.

84.

84. Czaja CA, Levin AR, Cox CW, Vargas D, Daley CL, Cott GR. Improvement in quality of life after therapy for Mycobacterium abscessus group lung infection: a prospective cohort study. Ann Am Thorac Soc 2016; 13:40-8.

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