Download PDF
Semin Respir Crit Care Med 2018; 39(03): 351-361
DOI: 10.1055/s-0038-1660472
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of Mycobacterium avium Complex (MAC)

David E. Griffith
1   Department of Medicine, University of Texas Health Science Center, Tyler, Texas
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2018 (online)

    Permissions and Reprints

Abstract

Mycobacterium avium complex (MAC) is the most commonly isolated nontuberculous mycobacterial respiratory pathogen worldwide. MAC lung disease is manifested either by fibrocavitary radiographic changes similar to pulmonary tuberculosis or by bronchiectasis with nodular and reticulonodular radiographic changes. This latter form of MAC lung disease, termed “nodular bronchiectatic (NB) MAC lung disease” is the most common form of MAC lung disease in the United States. Treatment at the time of diagnosis is always indicated for fibrocavitary MAC lung disease because it is always progressive and associated with increased morbidity and mortality compared with NB MAC lung disease. In contrast, the NB form of MAC lung disease is more indolent and frequently does not require antimycobacterial therapy. For patients with NB MAC lung disease, the priorities are typically to treat the underlying bronchiectasis and determine the course and impact of the MAC infection over time. Guidelines-based MAC therapy with multidrug regimens including macrolides is usually effective, but far from as predictably effective and durable as therapy for tuberculosis. It is imperative that clinicians are familiar with MAC drug resistance mechanisms and the pitfalls of inappropriate dependence on in vitro drug susceptibility testing which can predispose patients to the development of macrolide resistance with its attendant high mortality. It is now more than 20 years since the emergence of macrolides for MAC therapy with no new comparably effective agents introduced in that time, although one new inhaled amikacin therapy under study offers promise.

Keywords

Mycobacterium avium complex - treatment - mycobacteria - macrolide - bronchiectasis
 

  • References

  • 1 Tortoli E, Rindi L, Garcia MJ. , et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov. Int J Syst Evol Microbiol 2004; 54 (Pt 4): 1277-1285
    CrossrefPubMedGoogle Scholar
  • 2 Chand M, Lamagni T, Kranzer K. , et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis 2017; 64 (03) 335-342
    CrossrefPubMedGoogle Scholar
  • 3 Rindi L, Garzelli C. Genetic diversity and phylogeny of Mycobacterium avium . Infect Genet Evol 2014; 21: 375-383
    CrossrefPubMedGoogle Scholar
  • 4 Tran QT, Han XY. Subspecies identification and significance of 257 clinical strains of Mycobacterium avium . J Clin Microbiol 2014; 52 (04) 1201-1206
    CrossrefPubMedGoogle Scholar
  • 5 Koh WJ, Jeong BH, Jeon K. , et al. Clinical significance of the differentiation between Mycobacterium avium and Mycobacterium intracellulare in M. avium complex lung disease. Chest 2012; 142 (06) 1482-1488
    CrossrefPubMedGoogle Scholar
  • 6 Kim SY, Shin SH, Moon SM. , et al. Distribution and clinical significance of Mycobacterium avium complex species isolated from respiratory specimens. Diagn Microbiol Infect Dis 2017; 88 (02) 125-137
    CrossrefPubMedGoogle Scholar
  • 7 Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med 2015; 36 (01) 13-34
    CrossrefPubMedGoogle Scholar
  • 8 Hoefsloot W, van Ingen J, Andrejak C. , et al; Nontuberculous Mycobacteria Network European Trials Group. The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study. Eur Respir J 2013; 42 (06) 1604-1613
    CrossrefPubMedGoogle Scholar
  • 9 Ahn CH, Lowell JR, Onstad GD, Ahn SS, Hurst GA. Elimination of Mycobacterium intracellulare from sputum after bronchial hygiene. Chest 1979; 76 (04) 480-482
    CrossrefPubMedGoogle Scholar
  • 10 Prince DS, Peterson DD, Steiner RM. , et al. Infection with Mycobacterium avium complex in patients without predisposing conditions. N Engl J Med 1989; 321 (13) 863-868
    CrossrefPubMedGoogle Scholar
  • 11 Koh WJ, Kwon OJ, Jeon K. , et al. Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea. Chest 2006; 129 (02) 341-348
    CrossrefPubMedGoogle Scholar
  • 12 Lee G, Lee KS, Moon JW. , et al. Nodular bronchiectatic Mycobacterium avium complex pulmonary disease. Natural course on serial computed tomographic scans. Ann Am Thorac Soc 2013; 10 (04) 299-306
    CrossrefPubMedGoogle Scholar
  • 13 Andréjak C, Nielsen R, Thomsen VO, Duhaut P, Sørensen HT, Thomsen RW. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax 2013; 68 (03) 256-262
    CrossrefPubMedGoogle Scholar
  • 14 Brode SK, Campitelli MA, Kwong JC. , et al. The risk of mycobacterial infections associated with inhaled corticosteroid use. Eur Respir J 2017; 50 (03) 1700037
    CrossrefPubMedGoogle Scholar
  • 15 Koh WJ, Moon SM, Kim SY. , et al. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype. Eur Respir J 2017; 50 (03) 1602503
    CrossrefPubMedGoogle Scholar
  • 16 Fleshner M, Olivier KN, Shaw PA. , et al. Mortality among patients with pulmonary non-tuberculous mycobacteria disease. Int J Tuberc Lung Dis 2016; 20 (05) 582-587
    CrossrefPubMedGoogle Scholar
  • 17 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 (05) 575-583
    CrossrefPubMedGoogle Scholar
  • 18 Kumagai S, Ito A, Hashimoto T. , et al. Development and validation of a prognostic scoring model for Mycobacterium avium complex lung disease: an observational cohort study. BMC Infect Dis 2017; 17 (01) 436
    CrossrefPubMedGoogle Scholar
  • 19 Kim SJ, Yoon SH, Choi SM. , et al. Characteristics associated with progression in patients with of nontuberculous mycobacterial lung disease: a prospective cohort study. BMC Pulm Med 2017; 17 (01) 5
    CrossrefPubMedGoogle Scholar
  • 20 Lee MR, Yang CY, Chang KP. , et al. Factors associated with lung function decline in patients with non-tuberculous mycobacterial pulmonary disease. PLoS One 2013; 8 (03) e58214
    CrossrefPubMedGoogle Scholar
  • 21 Park TY, Chong S, Jung JW. , et al. Natural course of the nodular bronchiectatic form of Mycobacterium avium complex lung disease: long-term radiologic change without treatment. PLoS One 2017; 12 (10) e0185774
    CrossrefPubMedGoogle Scholar
  • 22 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 (06) 1222-1232
    CrossrefPubMedGoogle Scholar
  • 23 Pan SW, Shu CC, Feng JY. , 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 (06) 927-934
    CrossrefPubMedGoogle Scholar
  • 24 Diel R, Jacob J, Lampenius N. , et al. Burden of non-tuberculous mycobacterial pulmonary disease in Germany. Eur Respir J 2017; 49 (04) 1602109
    CrossrefPubMedGoogle Scholar
  • 25 van Ingen J, Boeree MJ, van Soolingen D, Mouton JW. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria. Drug Resist Updat 2012; 15 (03) 149-161
    CrossrefPubMedGoogle Scholar
  • 26 Brown-Elliott BA, Nash KA, Wallace Jr RJ. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev 2012; 25 (03) 545-582
    CrossrefPubMedGoogle Scholar
  • 27 Griffith DE, Brown-Elliott BA, Langsjoen B. , et al. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2006; 174 (08) 928-934
    CrossrefPubMedGoogle Scholar
  • 28 Brown-Elliott BA, Iakhiaeva E, Griffith DE. , et al. In vitro activity of amikacin against isolates of Mycobacterium avium complex with proposed MIC breakpoints and finding of a 16S rRNA gene mutation in treated isolates. J Clin Microbiol 2013; 51 (10) 3389-3394
    CrossrefPubMedGoogle Scholar
  • 29 Morimoto K, Namkoong H, Hasegawa N. , et al; Nontuberculous Mycobacteriosis Japan Research Consortium. Macrolide-resistant Mycobacterium avium complex lung disease: analysis of 102 consecutive cases. Ann Am Thorac Soc 2016; 13 (11) 1904-1911
    CrossrefPubMedGoogle Scholar
  • 30 Moon SM, Park HY, Kim SY. , et al. Clinical characteristics, treatment outcomes, and resistance mutations associated with macrolide-resistant Mycobacterium avium complex lung disease. Antimicrob Agents Chemother 2016; 60 (11) 6758-6765
    CrossrefPubMedGoogle Scholar
  • 31 Kadota T, Matsui H, Hirose T. , et al. Analysis of drug treatment outcome in clarithromycin-resistant Mycobacterium avium complex lung disease. BMC Infect Dis 2016; 16: 31
    CrossrefPubMedGoogle Scholar
  • 32 Griffith DE, Aksamit T, Brown-Elliott BA. , et al; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175 (04) 367-416 [Erratum: Am J Respir Crit Care Med. 2007 Apr 1;175(7):744–745 (Note: Dosage error in article text)]
    CrossrefPubMedGoogle Scholar
  • 33 van Ingen J, Egelund EF, Levin A. , et al. The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment. Am J Respir Crit Care Med 2012; 186 (06) 559-565
    CrossrefPubMedGoogle Scholar
  • 34 Wallace Jr RJ, Brown BA, Griffith DE, Girard W, Tanaka K. Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection. J Infect Dis 1995; 171 (03) 747-750
    CrossrefPubMedGoogle Scholar
  • 35 Koh WJ, Jeong BH, Jeon K, Lee SY, Shin SJ. Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2012; 186 (08) 797-802
    CrossrefPubMedGoogle Scholar
  • 36 Wallace Jr RJ, Brown-Elliott BA, McNulty S. , et al. Macrolide/Azalide therapy for nodular/bronchiectatic mycobacterium avium complex lung disease. Chest 2014; 146 (02) 276-282
    CrossrefPubMedGoogle Scholar
  • 37 Jeong BH, Jeon K, Park HY. , et al. Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2015; 191 (01) 96-103
    CrossrefPubMedGoogle Scholar
  • 38 Jhun BW, Moon SM, Kim SY. , et al. Intermittent antibiotic therapy for recurrent nodular bronchiectatic Mycobacterium avium complex lung disease. Antimicrob Agents Chemother 2018; 62 (02) e01812-e01817
    PubMedGoogle Scholar
  • 39 Mitchell JD, Bishop A, Cafaro A, Weyant MJ, Pomerantz M. Anatomic lung resection for nontuberculous mycobacterial disease. Ann Thorac Surg 2008; 85 (06) 1887-1892 , discussion 1892–1893
    CrossrefPubMedGoogle Scholar
  • 40 Mitchell JD. Surgical approach to pulmonary nontuberculous mycobacterial infections. Clin Chest Med 2015; 36 (01) 117-122
    PubMedGoogle Scholar
  • 41 Nelson KG, Griffith DE, Brown BA, Wallace Jr RJ. Results of operation in Mycobacterium avium-intracellulare lung disease. Ann Thorac Surg 1998; 66 (02) 325-330
    CrossrefPubMedGoogle Scholar
  • 42 Jarand J, Levin A, Zhang L, Huitt G, Mitchell JD, Daley CL. Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease. Clin Infect Dis 2011; 52 (05) 565-571
    CrossrefPubMedGoogle Scholar
  • 43 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 (01) 9-16
    CrossrefPubMedGoogle Scholar
  • 44 van Ingen J, Wagner D, Gallagher J. , et al; NTM-NET. Poor adherence to management guidelines in nontuberculous mycobacterial pulmonary diseases. Eur Respir J 2017; 49 (02) 1601855
    CrossrefPubMedGoogle Scholar
  • 45 Field SK, Cowie RL. Treatment of Mycobacterium avium-intracellulare complex lung disease with a macrolide, ethambutol, and clofazimine. Chest 2003; 124 (04) 1482-1486
    CrossrefPubMedGoogle Scholar
  • 46 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 (05) 1285-1293
    CrossrefPubMedGoogle Scholar
  • 47 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 (04) 800-809
    CrossrefPubMedGoogle Scholar
  • 48 Olivier KN, Shaw PA, Glaser TS. , et al. Inhaled amikacin for treatment of refractory pulmonary nontuberculous mycobacterial disease. Ann Am Thorac Soc 2014; 11 (01) 30-35
    CrossrefPubMedGoogle Scholar
  • 49 Yagi K, Ishii M, Namkoong H. , 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 (01) 558
    CrossrefPubMedGoogle Scholar
  • 50 Davis KK, Kao PN, Jacobs SS, Ruoss SJ. Aerosolized amikacin for treatment of pulmonary Mycobacterium avium infections: an observational case series. BMC Pulm Med 2007; 7: 2
    CrossrefPubMedGoogle Scholar
  • 51 Mukherjee V, Bender WS, Egan III JP. Inhaled antibiotics for refractory nontuberculous mycobacteria and non-cystic fibrosis bronchiectasis and the significance of Mycobacterium abscessus subsp. abscessus isolation during M. avium complex lung disease therapy. Am J Respir Crit Care Med 2015; 192 (01) 106-108
    CrossrefPubMedGoogle Scholar
  • 52 Olivier KN, Griffith DE, Eagle G. , et al. Randomized trial of liposomal amikacin for inhalation in nontuberculous mycobacterial lung disease. Am J Respir Crit Care Med 2017; 195 (06) 814-823
    CrossrefPubMedGoogle Scholar
  • 53 Seaworth BJ, Griffith DE. Therapy of multidrug-resistant and extensively drug-resistant tuberculosis. Microbiol Spectr 2017;5(2)
    PubMedGoogle Scholar
  • 54 Brown-Elliott BA, Philley JV, Griffith DE, Thakkar F, Wallace Jr RJ. In vitro susceptibility testing of bedaquiline against Mycobacterium avium complex. Antimicrob Agents Chemother 2017; 61 (02) e01798-16
    PubMedGoogle Scholar
  • 55 Philley JV, Wallace Jr RJ, Benwill JL. , et al. Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease. Chest 2015; 148 (02) 499-506
    CrossrefPubMedGoogle Scholar
  • 56 Griffith DE, Philley JV, Brown-Elliott BA. , et al. The significance of Mycobacterium abscessus subspecies abscessus isolation during Mycobacterium avium complex lung disease therapy. Chest 2015; 147 (05) 1369-1375
    CrossrefPubMedGoogle Scholar