Semin Respir Crit Care Med 2018; 39(03): 343-350
DOI: 10.1055/s-0038-1651493
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Diagnosis of Nontuberculous Mycobacteria Lung Disease

Steven A. Cowman
1   National Heart and Lung Institute, Imperial College London, London, United Kingdom
,
Michael R. Loebinger
2   Consultant Respiratory Physician, Royal Brompton Hospital, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2018 (online)

Abstract

The diagnosis of pulmonary nontuberculous mycobacteria (NTM) disease may be challenging, as their presence alone does not necessarily indicate disease and diagnosis requires the integration of clinical, radiological, and microbiological findings. The first step is to suspect NTM disease; however, clinical manifestations of NTM are nonspecific and it may not be possible to separate them from those caused by underlying respiratory disease. The radiological appearance generally falls into two patterns, fibrocavitary disease and nodular-bronchiectatic disease; consolidation, infiltrates, and solitary nodules are also described. The isolation of NTM from clinical samples is fundamental to the diagnosis and they may be cultured from sputum, bronchoalveolar lavage fluid, or tissue specimens. If sputum is used, more than one isolate is required for diagnosis due to the propensity of NTM to contaminate clinical samples. The correct identification of NTM is vital, as their clinical relevance varies widely between species, and treatment is dictated by the identity of the isolated organism. This review covers the clinical presentation of NTM disease, the interpretation of radiological findings, and issues surrounding the isolation and identification of mycobacteria.

 
  • References

  • 1 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
  • 2 Koh W-J, Chang B, Ko Y. , et al. Clinical significance of a single isolation of pathogenic nontuberculous mycobacteria from sputum specimens. Diagn Microbiol Infect Dis 2013; 75 (02) 225-226
  • 3 van Ingen J, Bendien SA, de Lange WCM. , et al. Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, The Netherlands. Thorax 2009; 64 (06) 502-506
  • 4 Jankovic M, Sabol I, Zmak L. , et al. Microbiological criteria in non-tuberculous mycobacteria pulmonary disease: a tool for diagnosis and epidemiology. Int J Tuberc Lung Dis 2016; 20 (07) 934-940
  • 5 Plotinsky RN, Talbot EA, von Reyn CF. Proposed definitions for epidemiologic and clinical studies of Mycobacterium avium complex pulmonary disease. PLoS One 2013; 8 (11) e77385
  • 6 Corbett EL, Blumberg L, Churchyard GJ. , et al. Nontuberculous mycobacteria: defining disease in a prospective cohort of South African miners. Am J Respir Crit Care Med 1999; 160 (01) 15-21
  • 7 Honda JR, Knight V, Chan ED. Pathogenesis and risk factors for nontuberculous mycobacterial lung disease. Clin Chest Med 2015; 36 (01) 1-11
  • 8 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
  • 9 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
  • 10 Reich JM, Johnson RE. Mycobacterium avium complex pulmonary disease presenting as an isolated lingular or middle lobe pattern. The Lady Windermere syndrome. Chest 1992; 101 (06) 1605-1609
  • 11 Iseman MD, Buschman DL, Ackerson LM. Pectus excavatum and scoliosis. Thoracic anomalies associated with pulmonary disease caused by Mycobacterium avium complex. Am Rev Respir Dis 1991; 144 (04) 914-916
  • 12 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
  • 13 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
  • 14 Griffith DE, Girard WM, Wallace Jr RJ. Clinical features of pulmonary disease caused by rapidly growing mycobacteria. An analysis of 154 patients. Am Rev Respir Dis 1993; 147 (05) 1271-1278
  • 15 Koh W-J, Kwon OJ, Jeon K. , et al. Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea. Chest 2006; 129 (02) 341-348
  • 16 Shitrit D, Peled N, Bishara J. , et al. Clinical and radiological features of Mycobacterium kansasii infection and Mycobacterium simiae infection. Respir Med 2008; 102 (11) 1598-1603
  • 17 Kobashi Y, Matsushima T, Oka M. A double-blind randomized study of aminoglycoside infusion with combined therapy for pulmonary Mycobacterium avium complex disease. Respir Med 2007; 101 (01) 130-138
  • 18 Andréjak C, Lescure F-X, Pukenyte E. , et al; Xenopi Group. Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France. Thorax 2009; 64 (04) 291-296
  • 19 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
  • 20 Shu C-C, Lee C-H, Hsu C-L. , et al; TAMI Group. Clinical characteristics and prognosis of nontuberculous mycobacterial lung disease with different radiographic patterns. Lung 2011; 189 (06) 467-474
  • 21 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
  • 22 Koh W-J, Jeong B-H, 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
  • 23 Miwa S, Shirai M, Toyoshima M. , et al. Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study. Ann Am Thorac Soc 2014; 11 (01) 23-29
  • 24 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 (08) e008058
  • 25 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
  • 26 Komiya K, Kurashima A, Ihi T. , et al. Long-term, low-dose erythromycin monotherapy for Mycobacterium avium complex lung disease: a propensity score analysis. Int J Antimicrob Agents 2014; 44 (02) 131-135
  • 27 Hwang JA, Kim S, Jo K-W, Shim TS. Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course. Eur Respir J 2017; 49 (03) 1600537
  • 28 Koh W-J, Yu CM, Suh GY. , et al. Pulmonary TB and NTM lung disease: comparison of characteristics in patients with AFB smear-positive sputum. Int J Tuberc Lung Dis 2006; 10 (09) 1001-1007
  • 29 Kendall BA, Varley CD, Choi D. , et al. Distinguishing tuberculosis from nontuberculous mycobacteria lung disease, Oregon, USA. Emerg Infect Dis 2011; 17 (03) 506-509
  • 30 Kim YK, Hahn S, Uh Y. , et al. Comparable characteristics of tuberculous and non-tuberculous mycobacterial cavitary lung diseases. Int J Tuberc Lung Dis 2014; 18 (06) 725-729
  • 31 Lee A-R, Lee J, Choi S-M. , et al. Phenotypic, immunologic, and clinical characteristics of patients with nontuberculous mycobacterial lung disease in Korea. BMC Infect Dis 2013; 13 (01) 558
  • 32 Hoefsloot W, van Ingen J, de Lange WC, Dekhuijzen PN, Boeree MJ, van Soolingen D. Clinical relevance of Mycobacterium malmoense isolation in The Netherlands. Eur Respir J 2009; 34 (04) 926-931
  • 33 Duan H, Han X, Wang Q. , et al. Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in a Chinese tuberculosis tertiary care center. Sci Rep 2016; 6: 36299
  • 34 Gubler JG, Salfinger M, von Graevenitz A. Pseudoepidemic of nontuberculous mycobacteria due to a contaminated bronchoscope cleaning machine. Report of an outbreak and review of the literature. Chest 1992; 101 (05) 1245-1249
  • 35 Tsukamura M. Diagnosis of disease caused by Mycobacterium avium complex. Chest 1991; 99 (03) 667-669
  • 36 Steingart KR, Henry M, Ng V. , et al. Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review. Lancet Infect Dis 2006; 6 (09) 570-581
  • 37 Wright PW, Wallace Jr RJ, Wright NW, Brown BA, Griffith DE. Sensitivity of fluorochrome microscopy for detection of Mycobacterium tuberculosis versus nontuberculous mycobacteria. J Clin Microbiol 1998; 36 (04) 1046-1049
  • 38 Zoumot Z, Boutou AK, Gill SS. , et al. Mycobacterium avium complex infection in non-cystic fibrosis bronchiectasis. Respirology 2014; 19 (05) 714-722
  • 39 Andréjak C, Thomsen VØ, Johansen IS. , et al. Nontuberculous pulmonary mycobacteriosis in Denmark: incidence and prognostic factors. Am J Respir Crit Care Med 2010; 181 (05) 514-521
  • 40 Rice JP, Seifert M, Moser KS, Rodwell TC. Performance of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis and rifampin resistance in a low-incidence, high-resource setting. PLoS One 2017; 12 (10) e0186139
  • 41 Luetkemeyer AF, Kendall MA, Wu X. , et al; Adult AIDS Clinical Trials Group A5255 Study Team. Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB. J Clin Microbiol 2014; 52 (04) 1052-1059
  • 42 Bicmen C, Gunduz AT, Coskun M, Senol G, Cirak AK, Ozsoz A. Molecular detection and identification of mycobacterium tuberculosis complex and four clinically important nontuberculous mycobacterial species in smear-negative clinical samples by the genotype mycobacteria direct test. J Clin Microbiol 2011; 49 (08) 2874-2878
  • 43 Haworth CS, Banks J, Capstick T. , et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax 2017; 72 (Suppl. 02) ii1-ii64
  • 44 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
  • 45 Bange FC, Böttger EC. Improved decontamination method for recovering mycobacteria from patients with cystic fibrosis. Eur J Clin Microbiol Infect Dis 2002; 21 (07) 546-548
  • 46 van Ingen J. Microbiological diagnosis of nontuberculous mycobacterial pulmonary disease. Clin Chest Med 2015; 36 (01) 43-54
  • 47 Cruciani M, Scarparo C, Malena M, Bosco O, Serpelloni G, Mengoli C. Meta-analysis of BACTEC MGIT 960 and BACTEC 460 TB, with or without solid media, for detection of mycobacteria. J Clin Microbiol 2004; 42 (05) 2321-2325
  • 48 Idigoras P, Beristain X, Iturzaeta A, Vicente D, Pérez-Trallero E. Comparison of the automated nonradiometric Bactec MGIT 960 system with Löwenstein-Jensen, Coletsos, and Middlebrook 7H11 solid media for recovery of mycobacteria. Eur J Clin Microbiol Infect Dis 2000; 19 (05) 350-354
  • 49 Lee JJ, Suo J, Lin CB, Wang JD, Lin TY, Tsai YC. Comparative evaluation of the BACTEC MGIT 960 system with solid medium for isolation of mycobacteria. Int J Tuberc Lung Dis 2003; 7 (06) 569-574
  • 50 Griffith DE, Adjemian J, Brown-Elliott BA. , et al. Semiquantitative culture analysis during therapy for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2015; 192 (06) 754-760
  • 51 Springer B, Stockman L, Teschner K, Roberts GD, Böttger EC. Two-laboratory collaborative study on identification of mycobacteria: molecular versus phenotypic methods. J Clin Microbiol 1996; 34 (02) 296-303
  • 52 Hoshino Y, Suzuki K. Differential diagnostic assays for discriminating mycobacteria, especially for nontuberculous mycobacteria: what does the future hold?. Future Microbiol 2015; 10 (02) 205-216
  • 53 Böddinghaus B, Rogall T, Flohr T, Blöcker H, Böttger EC. Detection and identification of mycobacteria by amplification of rRNA. J Clin Microbiol 1990; 28 (08) 1751-1759
  • 54 Kirschner P, Springer B, Vogel U. , et al. Genotypic identification of mycobacteria by nucleic acid sequence determination: report of a 2-year experience in a clinical laboratory. J Clin Microbiol 1993; 31 (11) 2882-2889
  • 55 Macheras E, Roux A-L, Ripoll F. , et al. Inaccuracy of single-target sequencing for discriminating species of the Mycobacterium abscessus group. J Clin Microbiol 2009; 47 (08) 2596-2600
  • 56 Telenti A, Marchesi F, Balz M, Bally F, Böttger EC, Bodmer T. Rapid identification of mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis. J Clin Microbiol 1993; 31 (02) 175-178
  • 57 Kim H, Kim SH, Shim TS. , et al. Differentiation of Mycobacterium species by analysis of the heat-shock protein 65 gene (hsp65). Int J Syst Evol Microbiol 2005; 55 (Pt 4): 1649-1656
  • 58 Adékambi T, Drancourt M, Raoult D. The rpoB gene as a tool for clinical microbiologists. Trends Microbiol 2009; 17 (01) 37-45
  • 59 Zelazny AM, Root JM, Shea YR. , et al. Cohort study of molecular identification and typing of Mycobacterium abscessus, Mycobacterium massiliense, and Mycobacterium bolletii . J Clin Microbiol 2009; 47 (07) 1985-1995
  • 60 Quan TP, Bawa Z, Foster D. , et al; MMM Informatics Group. Evaluation of whole-genome sequencing for mycobacterial species identification and drug susceptibility testing in a clinical setting: a large-scale prospective assessment of performance against line probe assays and phenotyping. J Clin Microbiol 2018; 56 (02) e01480-e17
  • 61 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
  • 62 Walker TM, Merker M, Kohl TA, Crook DW, Niemann S, Peto TEA. Whole genome sequencing for M/XDR tuberculosis surveillance and for resistance testing. Clin Microbiol Infect 2017; 23 (03) 161-166
  • 63 Clark AE, Kaleta EJ, Arora A, Wolk DM. Matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology. Clin Microbiol Rev 2013; 26 (03) 547-603
  • 64 Alcaide F, Amlerová J, Bou G. , et al; European Study Group on Genomics and Molecular Diagnosis (ESGMD). How to: identify non-tuberculous Mycobacterium species using MALDI-TOF mass spectrometry. Clin Microbiol Infect 2017; DOI: 10.1016/j.cmi.2017.11.012. [ Epub ahead of print]
  • 65 van Eck K, Faro D, Wattenberg M, de Jong A, Kuipers S, van Ingen J. Matrix-assisted laser desorption ionization-time of flight mass spectrometry fails to identify nontuberculous mycobacteria from primary cultures of respiratory samples. J Clin Microbiol 2016; 54 (07) 1915-1917
  • 66 Ellis SM, Hansell DM. Imaging of non-tuberculous (atypical) mycobacterial pulmonary infection. Clin Radiol 2002; 57 (08) 661-669
  • 67 Kwak N, Lee CH, Lee H-J. , et al. Non-tuberculous mycobacterial lung disease: diagnosis based on computed tomography of the chest. Eur Radiol 2016; 26 (12) 4449-4456
  • 68 Miller Jr WT, Miller WT. Pulmonary infections with atypical mycobacteria in the normal host. Semin Roentgenol 1993; 28 (02) 139-149
  • 69 Erasmus JJ, McAdams HP, Farrell MA, Patz Jr EF. Pulmonary nontuberculous mycobacterial infection: radiologic manifestations. Radiographics 1999; 19 (06) 1487-1505
  • 70 Char A, Hopkinson NS, Hansell DM. , et al. Evidence of mycobacterial disease in COPD patients with lung volume reduction surgery; the importance of histological assessment of specimens: a cohort study. BMC Pulm Med 2014; 14 (01) 124
  • 71 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
  • 72 Okumura M, Iwai K, Ogata H. , et al. Clinical factors on cavitary and nodular bronchiectatic types in pulmonary Mycobacterium avium complex disease. Intern Med 2008; 47 (16) 1465-1472
  • 73 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
  • 74 Hollings NP, Wells AU, Wilson R, Hansell DM. Comparative appearances of non-tuberculous mycobacteria species: a CT study. Eur Radiol 2002; 12 (09) 2211-2217
  • 75 Ellis SM. The spectrum of tuberculosis and non-tuberculous mycobacterial infection. Eur Radiol 2004; 14 (03) (Suppl. 03) E34-E42
  • 76 Kim C, Park SH, Oh SY. , et al. Comparison of chest CT findings in nontuberculous mycobacterial diseases vs. Mycobacterium tuberculosis lung disease in HIV-negative patients with cavities. PLoS One 2017; 12 (03) e0174240
  • 77 Watanabe M, Hasegawa N, Ishizaka A. , et al. Early pulmonary resection for Mycobacterium avium complex lung disease treated with macrolides and quinolones. Ann Thorac Surg 2006; 81 (06) 2026-2030
  • 78 O'Connell ML, Birkenkamp KE, Kleiner DE, Folio LR, Holland SM, Olivier KN. Lung manifestations in an autopsy-based series of pulmonary or disseminated nontuberculous mycobacterial disease. Chest 2012; 141 (05) 1203-1209
  • 79 Jeong YJ, Lee KS, Koh W-J, Han J, Kim TS, Kwon OJ. Nontuberculous mycobacterial pulmonary infection in immunocompetent patients: comparison of thin-section CT and histopathologic findings. Radiology 2004; 231 (03) 880-886
  • 80 Kitada S, Maekura R, Toyoshima N. , et al. Serodiagnosis of pulmonary disease due to Mycobacterium avium complex with an enzyme immunoassay that uses a mixture of glycopeptidolipid antigens. Clin Infect Dis 2002; 35 (11) 1328-1335
  • 81 Kitada S, Maekura R, Toyoshima N. , et al. Use of glycopeptidolipid core antigen for serodiagnosis of mycobacterium avium complex pulmonary disease in immunocompetent patients. Clin Diagn Lab Immunol 2005; 12 (01) 44-51
  • 82 Shibata Y, Horita N, Yamamoto M. , et al. Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta-analysis. Sci Rep 2016; 6 (01) 29325