Semin Respir Crit Care Med 2018; 39(03): 383-391
DOI: 10.1055/s-0038-1651495
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Nontuberculous Mycobacteria in Cystic Fibrosis

Brian S. Furukawa
1   Department of Medicine, Loma Linda University, Loma Linda, California
,
Patrick A. Flume
2   Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
3   Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2018 (online)

Abstract

Nontuberculous mycobacteria (NTM) can cause chronic pulmonary infection in susceptible hosts. Individuals with cystic fibrosis (CF), a multisystem disease predominated by progressive structural lung disease, are particularly vulnerable. Only recently have NTM been recognized for their potential to cause lung deterioration in CF patients. The reported prevalence varies widely from 4 to 40%, significantly more common than in the general population, but this varies because of multiple factors including inconsistent screening practices. Mycobacterium abscessus complex and Mycobacterium avium complex are the two most common species recovered. Defining NTM pulmonary disease in a CF patient can present challenges as it can be difficult to distinguish from the other potentially pathogenic organisms in the lung microbiome. In general, treatment regimens do not differ from the non-CF population but the clinician should be aware of potential interactions with other CF therapies. Recent population-level genomics has raised serious concern for indirect person-to-person transmission of several dominating NTM clones worldwide, raising awareness for increase prevention strategies when CF patients potentially congregate, such as clinic visits. Lung transplantation is controversial in those with NTM present in sputum culture but the available evidence suggests that this is not an absolute contraindication.

 
  • References

  • 1 Martiniano SL, Sontag MK, Daley CL, Nick JA, Sagel SD. Clinical significance of a first positive nontuberculous mycobacteria culture in cystic fibrosis. Ann Am Thorac Soc 2014; 11 (01) 36-44
  • 2 Cystic Fibrosis Foundation Patient Registry 2016 Annual Data Report. 2017. Available at: https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2016-Patient-Registry-Annual-Data-Report.pdf . Accessed November 13, 2017
  • 3 Goslee S, Wolinsky E. Water as a source of potentially pathogenic mycobacteria. Am Rev Respir Dis 1976; 113 (03) 287-292
  • 4 Wolinsky E, Rynearson TK. Mycobacteria in soil and their relation to disease-associated strains. Am Rev Respir Dis 1968; 97 (06) 1032-1037
  • 5 Gruft H, Falkinham III JO, Parker BC. Recent experience in the epidemiology of disease caused by atypical mycobacteria. Rev Infect Dis 1981; 3 (05) 990-996
  • 6 Falkinham III JO. Nontuberculous mycobacteria from household plumbing of patients with nontuberculous mycobacteria disease. Emerg Infect Dis 2011; 17 (03) 419-424
  • 7 Cowman S, Burns K, Benson S, Wilson R, Loebinger MR. The antimicrobial susceptibility of non-tuberculous mycobacteria. J Infect 2016; 72 (03) 324-331
  • 8 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
  • 9 Floto RA, Olivier KN, Saiman L. , et al; US Cystic Fibrosis Foundation and European Cystic Fibrosis Society. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax 2016; 71 (Suppl. 01) i1-i22
  • 10 Olivier KN, Weber DJ, Wallace Jr RJ. , et al; Nontuberculous Mycobacteria in Cystic Fibrosis Study Group. Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis. Am J Respir Crit Care Med 2003; 167 (06) 828-834
  • 11 Qvist T, Gilljam M, Jönsson B. , et al; Scandinavian Cystic Fibrosis Study Consortium (SCFSC). Epidemiology of nontuberculous mycobacteria among patients with cystic fibrosis in Scandinavia. J Cyst Fibros 2015; 14 (01) 46-52
  • 12 Pierre-Audigier C, Ferroni A, Sermet-Gaudelus I. , et al. Age-related prevalence and distribution of nontuberculous mycobacterial species among patients with cystic fibrosis. J Clin Microbiol 2005; 43 (07) 3467-3470
  • 13 Fauroux B, Delaisi B, Clément A. , et al. Mycobacterial lung disease in cystic fibrosis: a prospective study. Pediatr Infect Dis J 1997; 16 (04) 354-358
  • 14 Whittier S, Hopfer RL, Knowles MR, Gilligan PH. Improved recovery of mycobacteria from respiratory secretions of patients with cystic fibrosis. J Clin Microbiol 1993; 31 (04) 861-864
  • 15 Jönsson BE, Gilljam M, Lindblad A, Ridell M, Wold AE, Welinder-Olsson C. Molecular epidemiology of Mycobacterium abscessus, with focus on cystic fibrosis. J Clin Microbiol 2007; 45 (05) 1497-1504
  • 16 Bar-On O, Mussaffi H, Mei-Zahav M. , et al. Increasing nontuberculous mycobacteria infection in cystic fibrosis. J Cyst Fibros 2015; 14 (01) 53-62
  • 17 Olivier KN, Weber DJ, Lee JH. , et al; Nontuberculous Mycobacteria in Cystic Fibrosis Study Group. Nontuberculous mycobacteria. II: nested-cohort study of impact on cystic fibrosis lung disease. Am J Respir Crit Care Med 2003; 167 (06) 835-840
  • 18 Levy I, Grisaru-Soen G, Lerner-Geva L. , et al. Multicenter cross-sectional study of nontuberculous mycobacterial infections among cystic fibrosis patients, Israel. Emerg Infect Dis 2008; 14 (03) 378-384
  • 19 Seddon P, Fidler K, Raman S. , et al. Prevalence of nontuberculous mycobacteria in cystic fibrosis clinics, United Kingdom, 2009. Emerg Infect Dis 2013; 19 (07) 1128-1130
  • 20 Roux AL, Catherinot E, Ripoll F. , et al; Jean-Louis Herrmann for the OMA Group. Multicenter study of prevalence of nontuberculous mycobacteria in patients with cystic fibrosis in france. J Clin Microbiol 2009; 47 (12) 4124-4128
  • 21 Campos-Herrero MI, Chamizo FJ, Caminero JA, Gilarranz R, Cabrera G, Cuyás J. Nontuberculous mycobacteria in cystic fibrosis patients on the Island of Gran Canaria. A population study. J Infect Chemother 2016; 22 (08) 526-531
  • 22 Prevots DR, Shaw PA, Strickland D. , et al. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med 2010; 182 (07) 970-976
  • 23 Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med 2012; 185 (08) 881-886
  • 24 Sermet-Gaudelus I, Le Bourgeois M, Pierre-Audigier C. , et al. Mycobacterium abscessus and children with cystic fibrosis. Emerg Infect Dis 2003; 9 (12) 1587-1591
  • 25 Catherinot E, Roux AL, Vibet MA. , et al; OMA group. Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations. J Cyst Fibros 2013; 12 (01) 74-80
  • 26 Esther Jr CR, Esserman DA, Gilligan P, Kerr A, Noone PG. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis. J Cyst Fibros 2010; 9 (02) 117-123
  • 27 Binder AM, Adjemian J, Olivier KN, Prevots DR. Epidemiology of nontuberculous mycobacterial infections and associated chronic macrolide use among persons with cystic fibrosis. Am J Respir Crit Care Med 2013; 188 (07) 807-812
  • 28 Bouso JM, Burns JJ, Amin R, Livingston FR, Elidemir O. Household proximity to water and nontuberculous mycobacteria in children with cystic fibrosis. Pediatr Pulmonol 2017; 52 (03) 324-330
  • 29 Catherinot E, Roux AL, Vibet MA. , et al; OMA group. Inhaled therapies, azithromycin and Mycobacterium abscessus in cystic fibrosis patients. Eur Respir J 2013; 41 (05) 1101-1106
  • 30 Coolen N, Morand P, Martin C. , et al. Reduced risk of nontuberculous mycobacteria in cystic fibrosis adults receiving long-term azithromycin. J Cyst Fibros 2015; 14 (05) 594-599
  • 31 Mussaffi H, Rivlin J, Shalit I, Ephros M, Blau H. Nontuberculous mycobacteria in cystic fibrosis associated with allergic bronchopulmonary aspergillosis and steroid therapy. Eur Respir J 2005; 25 (02) 324-328
  • 32 Paugam A, Baixench MT, Demazes-Dufeu N. , et al. Characteristics and consequences of airway colonization by filamentous fungi in 201 adult patients with cystic fibrosis in France. Med Mycol 2010; 48 (Suppl. 01) S32-S36
  • 33 Viviani L, Harrison MJ, Zolin A, Haworth CS, Floto RA. Epidemiology of nontuberculous mycobacteria (NTM) amongst individuals with cystic fibrosis (CF). J Cyst Fibros 2016; 15 (05) 619-623
  • 34 Knutsen AP, Mueller KR, Levine AD, Chouhan B, Hutcheson PS, Slavin RG. Asp f I CD4+ TH2-like T-cell lines in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1994; 94 (2, Pt 1): 215-221
  • 35 Skov M, Poulsen LK, Koch C. Increased antigen-specific Th-2 response in allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis. Pediatr Pulmonol 1999; 27 (02) 74-79
  • 36 Rodman DM, Polis JM, Heltshe SL. , et al. Late diagnosis defines a unique population of long-term survivors of cystic fibrosis. Am J Respir Crit Care Med 2005; 171 (06) 621-626
  • 37 Saiman L, Marshall BC, Mayer-Hamblett N. , et al; Macrolide Study Group. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 2003; 290 (13) 1749-1756
  • 38 Saiman L, Mayer-Hamblett N, Campbell P, Marshall BC. ; Macrolide Study Group. Heterogeneity of treatment response to azithromycin in patients with cystic fibrosis. Am J Respir Crit Care Med 2005; 172 (08) 1008-1012
  • 39 Altenburg J, de Graaff CS, Stienstra Y. , et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA 2013; 309 (12) 1251-1259
  • 40 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
  • 41 Renna M, Schaffner C, Brown K. , et al. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection. J Clin Invest 2011; 121 (09) 3554-3563
  • 42 Adjemian J, Olivier KN, Seitz AE, Falkinham III JO, Holland SM, Prevots DR. Spatial clusters of nontuberculous mycobacterial lung disease in the United States. Am J Respir Crit Care Med 2012; 186 (06) 553-558
  • 43 Adjemian J, Olivier KN, Prevots DR. Nontuberculous mycobacteria among patients with cystic fibrosis in the United States: screening practices and environmental risk. Am J Respir Crit Care Med 2014; 190 (05) 581-586
  • 44 Ziedalski TM, Kao PN, Henig NR, Jacobs SS, Ruoss SJ. Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection. Chest 2006; 130 (04) 995-1002
  • 45 Kim RD, Greenberg DE, Ehrmantraut ME. , et al. Pulmonary nontuberculous mycobacterial disease: prospective study of a distinct preexisting syndrome. Am J Respir Crit Care Med 2008; 178 (10) 1066-1074
  • 46 Esther Jr CR, Henry MM, Molina PL, Leigh MW. Nontuberculous mycobacterial infection in young children with cystic fibrosis. Pediatr Pulmonol 2005; 40 (01) 39-44
  • 47 Griffith DE. Emergence of nontuberculous mycobacteria as pathogens in cystic fibrosis. Am J Respir Crit Care Med 2003; 167 (06) 810-812
  • 48 Sanguinetti M, Ardito F, Fiscarelli E. , et al. Fatal pulmonary infection due to multidrug-resistant Mycobacterium abscessus in a patient with cystic fibrosis. J Clin Microbiol 2001; 39 (02) 816-819
  • 49 Verregghen M, Heijerman HG, Reijers M, van Ingen J, van der Ent CK. Risk factors for Mycobacterium abscessus infection in cystic fibrosis patients; a case-control study. J Cyst Fibros 2012; 11 (04) 340-343
  • 50 Qvist T, Taylor-Robinson D, Waldmann E. , et al. Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis. J Cyst Fibros 2016; 15 (03) 380-385
  • 51 Gilljam M, Berning SE, Peloquin CA, Strandvik B, Larsson LO. Therapeutic drug monitoring in patients with cystic fibrosis and mycobacterial disease. Eur Respir J 1999; 14 (02) 347-351
  • 52 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
  • 53 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
  • 54 Hafner R, Bethel J, Power M. , et al. Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers. Antimicrob Agents Chemother 1998; 42 (03) 631-639
  • 55 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
  • 56 Koh WJ, Kim YH, Kwon OJ. , et al. Surgical treatment of pulmonary diseases due to nontuberculous mycobacteria. J Korean Med Sci 2008; 23 (03) 397-401
  • 57 Ferro BE, Meletiadis J, Wattenberg M. , et al. Clofazimine prevents the regrowth of Mycobacterium abscessus and Mycobacterium avium type strains exposed to amikacin and clarithromycin. Antimicrob Agents Chemother 2015; 60 (02) 1097-1105
  • 58 Zuckerman JM, Qamar F, Bono BR. Review of macrolides (azithromycin, clarithromycin), ketolids (telithromycin) and glycylcyclines (tigecycline). Med Clin North Am 2011; 95 (04) 761-791 , viii
  • 59 Quon BS, Goss CH, Ramsey BW. Inhaled antibiotics for lower airway infections. Ann Am Thorac Soc 2014; 11 (03) 425-434
  • 60 Colin AA. Eradication of mycobacterium abscessus in a chronically infected patient with cystic fibrosis. Pediatr Pulmonol 2000; 30 (03) 267-268
  • 61 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
  • 62 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
  • 63 Meers P, Neville M, Malinin V. , et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother 2008; 61 (04) 859-868
  • 64 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 (09) e108703
  • 65 Jeong BH, Jeon K, Park HY. , et al. Peak plasma concentration of azithromycin and treatment responses in Mycobacterium avium complex lung disease. Antimicrob Agents Chemother 2016; 60 (10) 6076-6083
  • 66 Jordan CL, Noah TL, Henry MM. Therapeutic challenges posed by critical drug-drug interactions in cystic fibrosis. Pediatr Pulmonol 2016; 51 (S44): S61-S70
  • 67 Fohner AE, McDonagh EM, Clancy JP, Whirl Carrillo M, Altman RB, Klein TE. PharmGKB summary: ivacaftor pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics 2017; 27 (01) 39-42
  • 68 Talamo Guevara M, McColley SA. The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis. Expert Opin Drug Saf 2017; 16 (11) 1305-1311
  • 69 Maurer FP, Castelberg C, Quiblier C, Böttger EC, Somoskövi A. Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus. J Antimicrob Chemother 2014; 69 (06) 1559-1563
  • 70 Kim HY, Kim BJ, Kook Y. , et al. Mycobacterium massiliense is differentiated from Mycobacterium abscessus and Mycobacterium bolletii by erythromycin ribosome methyltransferase gene (erm) and clarithromycin susceptibility patterns. Microbiol Immunol 2010; 54 (06) 347-353
  • 71 Choi GE, Shin SJ, Won CJ. , et al. Macrolide treatment for Mycobacterium abscessus and Mycobacterium massiliense infection and inducible resistance. Am J Respir Crit Care Med 2012; 186 (09) 917-925
  • 72 Koh WJ, Jeon K, Lee NY. , et al. Clinical significance of differentiation of Mycobacterium massiliense from Mycobacterium abscessus. Am J Respir Crit Care Med 2011; 183 (03) 405-410
  • 73 DaCosta A, Jordan CL, Giddings O, Lin FC, Gilligan P, Esther Jr CR. Outcomes associated with antibiotic regimens for treatment of Mycobacterium abscessus in cystic fibrosis patients. J Cyst Fibros 2017; 16 (04) 483-487
  • 74 Bange FC, Brown BA, Smaczny C, Wallace Jr RJ, Böttger EC. Lack of transmission of mycobacterium abscessus among patients with cystic fibrosis attending a single clinic. Clin Infect Dis 2001; 32 (11) 1648-1650
  • 75 Aitken ML, Limaye A, Pottinger P. , et al. Respiratory outbreak of Mycobacterium abscessus subspecies massiliense in a lung transplant and cystic fibrosis center. Am J Respir Crit Care Med 2012; 185 (02) 231-232
  • 76 Bryant JM, Grogono DM, Greaves D. , et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet 2013; 381 (9877): 1551-1560
  • 77 Bryant JM, Grogono DM, Rodriguez-Rincon D. , et al. Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium. Science 2016; 354 (6313): 751-757
  • 78 Whitson BA, Hayes Jr D. Indications and outcomes in adult lung transplantation. J Thorac Dis 2014; 6 (08) 1018-1023
  • 79 Chalermskulrat W, Sood N, Neuringer IP. , et al. Non-tuberculous mycobacteria in end stage cystic fibrosis: implications for lung transplantation. Thorax 2006; 61 (06) 507-513
  • 80 Qvist T, Pressler T, Thomsen VO, Skov M, Iversen M, Katzenstein TL. Nontuberculous mycobacterial disease is not a contraindication to lung transplantation in patients with cystic fibrosis: a retrospective analysis in a Danish patient population. Transplant Proc 2013; 45 (01) 342-345
  • 81 Taylor JL, Palmer SM. Mycobacterium abscessus chest wall and pulmonary infection in a cystic fibrosis lung transplant recipient. J Heart Lung Transplant 2006; 25 (08) 985-988
  • 82 Chernenko SM, Humar A, Hutcheon M. , et al. Mycobacterium abscessus infections in lung transplant recipients: the international experience. J Heart Lung Transplant 2006; 25 (12) 1447-1455
  • 83 Roux AL, Catherinot E, Soismier N. , et al; OMA group. Comparing Mycobacterium massiliense and Mycobacterium abscessus lung infections in cystic fibrosis patients. J Cyst Fibros 2015; 14 (01) 63-69
  • 84 Knoll BM, Kappagoda S, Gill RR. , et al. Non-tuberculous mycobacterial infection among lung transplant recipients: a 15-year cohort study. Transpl Infect Dis 2012; 14 (05) 452-460
  • 85 Longworth SA, Vinnard C, Lee I, Sims KD, Barton TD, Blumberg EA. Risk factors for nontuberculous mycobacterial infections in solid organ transplant recipients: a case-control study. Transpl Infect Dis 2014; 16 (01) 76-83
  • 86 Lobo LJ, Noone PG. Respiratory infections in patients with cystic fibrosis undergoing lung transplantation. Lancet Respir Med 2014; 2 (01) 73-82
  • 87 Griffiths KJ. Experience of Mycobacterium abscessus eradication therapy at Aberdeen Royal Infirmary. J Cyst Fibros 2015; (Suppl. 01) S126
  • 88 Taccetti G, Campana S, Festini F, Mascherini M, Döring G. Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients. Eur Respir J 2005; 26 (03) 458-461
  • 89 Qvist T, Pressler T, Taylor-Robinson D, Katzenstein TL, Høiby N. Serodiagnosis of Mycobacterium abscessus complex infection in cystic fibrosis. Eur Respir J 2015; 46 (03) 707-716
  • 90 Heslet L, Bay C, Nepper-Christensen S. The immunomodulatory effect of inhaled granulocyte-macrophage colony-stimulating factor in cystic fibrosis. A new treatment paradigm. J Inflamm Res 2012; 5: 19-27
  • 91 Scott JP, Ji Y, Kannan M, Wylam ME. Inhaled granulocyte-macrophage colony-stimulating factor for Mycobacterium abscessus in cystic fibrosis. Eur Respir J 2018; 51 (04) pii