Emerging and Difficult to Treat Nontuberculous Mycobacteria Infections

  • I. W. Fong
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)


Nontuberculous mycobacteria [NTM] are a large group of environmental organisms [>150 species] that are distributed worldwide, but only a few are pathogenic and known to cause human diseases. They are widely distributed in waterways and soil and susceptible people become infected mainly from repeated inhalation of bioaerosols. The global epidemiology of NTM infections is not well delineated as they are not reportable to public health services, but the incidence of NTM lung disease is increasing in the United States and in many other countries. Chronic, debilitating lung disease is the most common manifestations of NTM infections. Of concern is the global outbreak of the novel mycobacteria, Mycobacterium chimaera, from contaminated heater cooler units in cardiac surgery units resulting in cardiac and extracardiac diseases or manifestations. Mycobacterium abscessus complex infections, primarily cause disease in the immunosuppressed with pulmonary or extrapulmonary infections, are the most difficult to treat due to its multidrug resistance pattern. This chapter will review Mycobacterium avium complex [MAC] lung infections, M. abscessus and M. chimaera infections.


Atypical mycobacteria Nontuberculous mycobacteria M. abscessus M. avium complex M. chimaera M. chelonae Pulmonary disease Disseminated disease Cervical lymphadenitis 


  1. 1.
    Honda JR, Virdi R, Chan ED (2018) Global environmental nontuberculous mycobacteria and their contemporaneous man-made and natural niches. Front Microbiol 9:2029PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Falkinham JO III (2013) Ecology of nontuberculous mycobacteria-where do human infections come from? Semin Respir Crit Care Med 34:95–102PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Adejemian J, Olivier KN, Seitz AE, Falkinham JO III, Holland SM, Prevosts DR (2012) Spatial clusters of nontuberculous mycobacteria lung disease in the United States. Am J Respir Crit Care Med 186:553–558CrossRefGoogle Scholar
  4. 4.
    Forbes BA, Hall GS, Miller MB et al (2018) Practice guidelines for clinical microbiology laboratories: mycobacteria. Clin Microbiol Rev 31:e00038–e00017PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Tortoli E (2014) Microbiological features and clinical relevance of new species of the genus Mycobacterium. Clin Microbiol Rev 27(4):727–752. Scholar
  6. 6.
    Prevots DR, Marrras TK (2015) Epidemiology of human pulmonary infection with non-tuberculous mycobacteria: a review. Clin Chest Med 36:13–34PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Lee H, Myung W, Koh W-J, Moon SM, Jhun BW (2019) Epidemiology of nontuberculous mycobacteria infection, South Korea, 2007-2016. Emerg Infect Dis 25:569–572. Scholar
  8. 8.
    Namkoong H, Kurashima A, Morimoto K et al (2016) Epidemiology of pulmonary nontuberculous mycobacterial disease. Jpn Emerg Infect Dis 22:1116–1117CrossRefGoogle Scholar
  9. 9.
    Jing H, Wang H, Wang Y et al (2012) Prevalence of nontuberculous mycobacteria infection, China, 2004-2009. Emerg Infect Dis 18:527–528PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Chetchotisakd P, Mootsikapun P, Anunnatsiri S et al (2000) Disseminated infection due to rapid growing mycobacteria in immunocompetent hosts presenting with chronic lymphadenopathy: a previously unrecognized clinical entity. Clin Infect Dis 30:29–34PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Rosenzweig SD, Holland SM (2005) Defects in the interferon-gamma and interleukin pathways. Immunol Rev 203:29–34CrossRefGoogle Scholar
  12. 12.
    Prince DS, Peterson DD, Steiner RM, Gottlieb JE, Scott R, Israel HL, Figueroa WG, Fish JE (1989) Infection with Mycobacterium avium complex in patients without predisposing conditions. N Engl J Med 321:863–868PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Kim RD, Greenberg DE, Ehrmantraut ME et al (2008) Pulmonary nontuberculous mycobacterial disease. Prospective study of a distinct preexisting syndrome. Am J Respir Crit Care Med 178:1066–1074PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Schorey JS, Sweet L (2008) The mycobacterial glycopeptidolipids: structure, function, and their role in pathogenesis. Glycobiology 18:832–841PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Busatto C, Vianna JS, da Silva Junior LV, Ramis IB, Almeida da Silva PE (2019) Mycobacterium avium: an overview. Tuberculosis 114:127–134PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Chatterjee D, Khoo KH (2001) The surface glycopeptidolipids of mycobacteria: structures and biological properties. Cell Mol Life Sci 58:2018–2042PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Maekura R, Okuda Y, Hirotani A et al (2005) Clinical and prognostic importance of serotyping Mycobacterium avium-Mycobacterium intracellulare complex isolates in human immunodeficiency virus-negative patients. J Clin Microbiol 43:3150–3158PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Carter G, Wu M, Drummond DC, Bermudez LE (2003) Characterization of biofilm formation by clinical isolates of Mycobacterium avium. J Med Microbiol 52:747–752PubMedCrossRefGoogle Scholar
  19. 19.
    Lake MA, Ambrose LR, Lipman MCI, Lowe DM (2016) “Why me, why now?” using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection. BMC Med 14:54PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Casanova J-L, Abel L (2004) The human model: a genetic dissection to infection in natural conditions. Nat Rev Immunol 4:55–66PubMedCrossRefGoogle Scholar
  21. 21.
    Embil J, Warren P, Yakrus M, Stark R, Corne S, Forrest D, Hershfield E (1997) Pulmonary illness associated with exposure to Mycobacterium avium complex in hot tub water. Chest 111:813–816PubMedCrossRefGoogle Scholar
  22. 22.
    Stout JE, Koh W-J, Yew WW (2016) Update on pulmonary disease due to non-tuberculous mycobacteria. Int J Infect Dis 45:123–134PubMedCrossRefGoogle Scholar
  23. 23.
    Daley C (2017) Mycobacterium avium complex disease. Microbiol Spectr 5(2):TNM17-0045-2017. Scholar
  24. 24.
    Buchacz K, Lau B, Jing Y et al (2016) Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, 2000-2010. J Infect Dis 214:862–872PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Yoo J-W, Jo K-W, Kim S-H et al (2016) Incidence, characteristics, and treatment outcomes of mycobacterial diseases in transplant recipients. Transpl Int 29:549–558PubMedCrossRefGoogle Scholar
  26. 26.
    Horsburgh CR Jr, Metchock B, Gordon SM, Havlik JA Jr, McGowan JE Jr, Thompson SE III (1994) Predictors of survival in patients with AIDS and disseminated Mycobacterium avium complex disease. J Infect Dis 170:573–577PubMedCrossRefGoogle Scholar
  27. 27.
    Chin DP, Reingold AL, Stone EN et al (1994) The impact of Mycobacterium avium complex bacteremia and its treatment on survival of AIDS patients—a prospective study. J Infect Dis 170:578–584PubMedCrossRefGoogle Scholar
  28. 28.
    Schon T, Chryssanthou E (2017) Minimum inhibitory concentration distribution for Mycobacterium avium complex-towards evidence-based susceptibility breakpoints. Int J Infect Dis 55:122–124PubMedCrossRefGoogle Scholar
  29. 29.
    Brown-Elliott BA, Woods GL (2019) Mini review: antimycobacterial susceptibility testing of nontuberculous mycobacteria. J Clin Microbiol 57(10):e00834-19. Scholar
  30. 30.
    Huang CC, Wu MF, Chen HC, Huang WC (2018) In vitro activity of aminoglycosides, clofazimine, d-cycloserine and dapsone against 83 Mycobacterium avium complex clinical isolates. J Microbiol Immunol Infect 51:636–643PubMedCrossRefGoogle Scholar
  31. 31.
    Rodrigues L, Sampaio D, Couto I, Machado D, Keru WV, Amaral L, Viveiros M (2009) The role of efflux pumps in macrolide resistance in Mycobacterium avium complex. Int J Antimicrob Agents Chemother 34:529–533CrossRefGoogle Scholar
  32. 32.
    van Ingren J, Boeree MJ, van Soolingen D, Moutton JW (2012) Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria. Drug Resist Updat 15:149–161CrossRefGoogle Scholar
  33. 33.
    Brown-Elliott BA, Nash KA, Wallace RJ Jr (2012) Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev 25:545–582PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Lee G, Lee KS, Moon JW, Koh WJ, Jeong BH, Jeong YJ, Woo S (2013) Nodular bronchiectatic Mycobacterium avium complex pulmonary disease. Natural course on serial computed tomographic scans. Ann Am Thorac Soc 10:299–306PubMedCrossRefGoogle Scholar
  35. 35.
    Kwon BS, Lee JH, Koh Y et al (2019) The natural history of non-cavitary nodular bronchiectatic Mycobacterium avium complex lung disease. Respir Med 150:45–50PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Pan S-W, Shu C-C, Feng J-H, Wang J-Y, Chan Y-J, Yu C-J, Su W-J (2017) Microbiological persistence in patients with Mycobacterium avium complex lung disease: the predictors and the impact on radiographic progression. Clin Infect Dis 65:927–934PubMedCrossRefGoogle Scholar
  37. 37.
    Kobashi Y, Matsuushima T, Oka M (2007) A double-blind randomized study of aminoglycoside infusion with combined therapy for pulmonary Mycobacterium avium complex disease. Respir Med 101:130–138PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Kim O-H, Kwon BS, Han M et al (2019) Association between duration of aminoglycoside treatment and outcome of cavitary Mycobacterium avium complex lung disease. Clin Infect Dis 68:1870–1876PubMedGoogle Scholar
  39. 39.
    Griffith DF, Aksamit T, Brown-Elliott BA et al (2007) An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial disease. Am J Repir Crit Care Med 175:367–416CrossRefGoogle Scholar
  40. 40.
    Jeong BH, Jeon K, Park HY et al (2015) Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 191:96–103PubMedCrossRefGoogle Scholar
  41. 41.
    Luo J, Yu X, Jiang G et al (2018) In vitro activity of clofazimine against nontuberculous mycobacteria isolated in Beijing, China. Antimicrob Agents Chemother 62:e00072-18PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Field SK, Cowie RL (2003) Treatment of Mycobacterium avium –intracellulare complex lung disease with a macrolide, ethambutol and clofazimine. Chest 124:1482–1486PubMedCrossRefGoogle Scholar
  43. 43.
    Jarand J, Davis JD, Cowie RL, Field SK, Fisher DA (2016) Long-term follow-up of Mycobacterium avium complex lung disease in patients treated with regimens including clofazimine and/or rifampin. Chest 149:1285–1293PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Koh W-J, Moon SM, Kim S-Y et al (2017) Outcomes of Mycobacterial avium complex lung disease based on clinical phenotype. Eur Repir J 50:1602503. Scholar
  45. 45.
    Field SK, Fisher D, Cowie RL (2004) Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest 126:566–581PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Kwak N, Park J, Kim E, Lee C-H, Han SK, Yim J-J (2017) Treatment outcomes of Mycobacterium avium complex lung disease: a systematic review and meta-analysis. Clin Infect Dis 65:1077–1084PubMedCrossRefGoogle Scholar
  47. 47.
    Miwa S, Shira M, Toyoshima M et al (2014) Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study. Ann Am Thorac Soc 11:23–29PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Jhun BW, Kim SY, Moon SM et al (2018) Development of macrolide resistance and reinfection in refractory Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 198:1322–1330PubMedCrossRefGoogle Scholar
  49. 49.
    McCoy CE (2018) Understanding the use of composite endpoints in clinical trials. West J Emerg Med 19:641–644CrossRefGoogle Scholar
  50. 50.
    Gochi M, Takayanagi N, Kanaauchi T, Ishiguro T, Yanagisawa T, Sugita Y (2015) Retrospective study of the predictors of mortality and radiographic deterioration in 782 patients with nodular/bronchiectatic Mycobacterium avium complex lung disease. BMJ Open 5(8):e008058PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Srivastava S, Deshpande D, Gumbo T (2017) Failure of the azithromycin and ethambutol combination regimen in the hollow-fiber system model of pulmonary Mycobacterium avium infection is due to acquired resistance. J Antimicrob Chemother 72(Suppl 2):120–123Google Scholar
  52. 52.
    Griffith DE, Eagle G, Thompson R et al (2018) 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 09:14Google Scholar
  53. 53.
    Collins LF, Clement ME, Stout JE (2017) Incidence, long-term outcomes, and healthcare utilization of patients with human immunodeficiency virus/acquired immune deficiency syndrome and disseminated Mycobacterium avium complex from 1992-2015. Open Forum Infect Dis 4(3):ofx120PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Kobayashi T, Nishijima T, Teruya K, Aoki T, Kikuchi Y, Oka S, Gatanaga H (2016) High mortality of disseminated non-tuberculous mycobacteria in HIV-infected patients in the retroviral era. PLoS One 11:e0151682PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Gordin FM, Sullam PM, Shafram SD, Cohn DL, Wynee B, Paxton L, Perry K, Horsbururgh CR Jr (1999) A randomized, placebo-controlled study of rifabutin added to a regimen of clarithromycin and ethambutol for treatment of disseminated infection with Mycobacterium avium complex. Clin Infect Dis 28:1080–1085PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Benson CA, Williams PL, Currier JS et al (2003) A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. Clin Infect Dis 37:1234–1243PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Lee MR, Chien JY, Huang YT et al (2017) Clinical features of patients with bacteremia caused by Mycobacterium avium complex species and antimicrobial susceptibility of the isolates at a medical center in Taiwan, 2008-2014. Int J Antimicrob Agents Chemother 50:35–40CrossRefGoogle Scholar
  58. 58.
    Hedary M, Nasiri MJ, Mirsaeidi M, Jazi FM, Khoshnood S, Drancourt M, Darban-Sarokhalil D (2019) Mycobacterium avium complex infection in patients with human immunodeficiency virus: a systematic review and meta-analysis. J Cell Physiol 234:9994–10001CrossRefGoogle Scholar
  59. 59.
    Sridhar S, Fung KSC, Chan JFW et al (2016) High recurrence rate supports need for secondary prophylaxis in non-HIV patients with disseminated Mycobacterium avium complex infection: a multicenter observational study. BMC Infect Dis 16:74PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Holland SM, Eisenstein EM, Kuhns DB, Turner ML, Fleisher TA, Strober W, Gallin JI (1994) Treatment of refractory disseminated mycobacterial infection with interferon gamma. A preliminary report. N Engl J Med 330:1348–1355PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Koh W-J (2017) Nontuberculous mycobacteria—overview. Microbiol Spectr 5(1):TNM17-0024-2016. Scholar
  62. 62.
    Christensen JB, Koeppe J (2010) Mycobacterium avium complex cervical lymphadenitis in an immunocompetent adult. Clin Vaccine Immunol 17:1488–1490PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Blyth C, Best E, Jones C, Nurse C, Goldwater P, Daley A, Burgner D, Henry G, Palsanthiran P (2009) Nontuberculous mycobacterial infection in children: a prospective study. Pediatr Infect Dis J 28:801–805PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Panesar J, Higgins K, Daya H, Forte V, Allen U (2003) Nontuberculous mycobacterial cervical adenitis: a ten-year retrospective review. Laryngoscope 113:149–154PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Lindeboom JA, Kuijper EJ, van Coppenraet B, Lindeboom R, Prins JM (2007) Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children: a multicenter, randomized, controlled trial. Clin Infect Dis 44:1057–1064PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Liondeboom JA (2011) Conservative wait-and-see therapy versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children. Clin Infect Dis 52:180–184CrossRefGoogle Scholar
  67. 67.
    Hatakeyama S, Ohama Y, Okazaki M, Nuku Y, Moriya K (2017) Antimicrobial susceptibility testing of rapidly growing mycobacteria isolated in Japan. BMC Infect Dis 17:197PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Pang H, Li G, Zhao X, Liu H, Wan K, Yu P (2015) Drug susceptibility testing of 31 antimicrobial agents on rapidly growing mycobacteria isolates from China. Biomed Res Int 2015:419392. Scholar
  69. 69.
    De Groote MA, Huitt G (2006) Infections due to rapidly growing mycobacteria. Clin Infect Dis 42:175663CrossRefGoogle Scholar
  70. 70.
    Han XY, De I, Jacobson KL (2007) Rapidly growing mycobacteria. Clinical and microbiological studies of 115 cases. Am J Clin Pathol 128:612–621PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Shen Y, Wang X, Jin W, Zhang X, Chen J, Zhang W (2018) In vitro susceptibility of Mycobacterium abscessus and Mycobacterium fortuitum isolates to 30 antibiotics. Biomed Res Int 2018:4902941. Scholar
  72. 72.
    Aziz DB, Law JL, Wu M-L, Gengenbacher M, Teo JW, Dartois V, Dick T (2017) Rifabutin is active against Mycobacterium abscessus complex. Antimicrob Agents Chemother 61:e00155–e00117PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Singh S, Bouzinbi N, Chaturvedi V, Godreuil S, Kremer L (2014) In vitro evaluation of a new combination against clinical isolates belonging to the Mycobacterium abscessus complex. Clin Microbiol Infect 20:01124–01127CrossRefGoogle Scholar
  74. 74.
    Shen G-H, Wu B-D, Hu S-T, Lin C-F, Wu K-M, Chen J-H (2010) High efficacy of clofazimine and its synergistic effect with amikacin against rapidly growing mycobacteria. Int J Antimicrob Agents 35:400–404PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Luthra S, Romanski A, Sanders P (2018) The role of antibiotic-target-modifying and antibiotic-modifying enzymes in Mycobacterium abscessus drug resistance. Front Microbiol 9:2179PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Pandry R, Chen L, Manca C et al (2019) Dual β-lactam combinations highly active against Mycobacterium abscessus complex in vitro. MBio 10:e02895-18. Scholar
  77. 77.
    Kumar P, Chauhan V, Silva JRA et al (2017) Mycobacterium abscessus L,D-transpeptidases are susceptible to inactivation by carbapenems and cephalosporins but not penicillins. Antimicrob Agents Chemother 61:e008666-17Google Scholar
  78. 78.
    Soroka D, Ourghanlian C, Compain F et al (2017) Inhibition of β-lactamases of mycobacteria by avibactum and clavulanate. J Antimicrob Chemother 72:1081–1088PubMedPubMedCentralGoogle Scholar
  79. 79.
    Lefebvre A-L, Moigne VL, Bermut A et al (2017) Inhibition of the β-lactamase BlaMab by avibactam improves the in vitro and in vivo efficacy of imipenem against Mycobacterium abscessus. Antimicrob Agents Chemother 61:e02440-16. Scholar
  80. 80.
    Deshpande D, Srivastava S, Chapagain ML, Lee PS, Cirrincione KN, Pasipanadya JG, Gumbo T (2017) The discovery of cetazidime/avibactam as an anti-Mycobacterium avium agent. J Antimicrob Chemother 72(Suppl 2):ii36–ii42CrossRefGoogle Scholar
  81. 81.
    Prammananan T, Sander P, Brown BA, Frischkorn K, Go O, Zhang Y, Bottger EC, Wallace RJ Jr (1998) A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptoamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae. J Infect Dis 177:1573–1581PubMedCrossRefGoogle Scholar
  82. 82.
    Nash KA, Andini N, Zhang Y, Brown-Elliott BA, Wallace RJ Jr (2006) Intrinsic resistance in rapidly growing mycobacteria. Antimicrob Agents Chemother 50:3476–3478PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Lee M-R, Sheng W-H, Hung C-C, Yu C-J, Lee L-N, Hsueh P-R (2016) Mycobacterium abscessus complex infections in humans. Emerg Infect Dis 21:1638–1646Google Scholar
  84. 84.
  85. 85.
    Steir M, Walsh M, Rosa R et al (2018) Mycobacterium abscessus complex infections: a retrospective cohort study. Open Forum Infect Dis 5(2):ofy022. Scholar
  86. 86.
    Lai CC, Tam CK, Chou CH et al (2010) Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000-2008. Emerg Infect Dis 16:294–296PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Benwell JL, Wallace RJ Jr (2014) Mycobacterium abscessus challenges in diagnosis and treatment. Curr Opin Infect Dis 27:506–510CrossRefGoogle Scholar
  88. 88.
    Byrant JM, Grogono DM, Greaves D et al (2013) Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective study. Lancet 381:1551–1560CrossRefGoogle Scholar
  89. 89.
    Esther CR Jr, Esserman DA, Gilligan P et al (2010) Chronic Mycobacterium abscessus infection and lung decline in cystic fibrosis. J Cyst Fibros 9:117–123PubMedCrossRefGoogle Scholar
  90. 90.
    Benwell JL, Wallace JL Jr (2014) Mycobacterium abscessus: challenges in diagnosis and treatment. Curr Opin Infect Dis 27:506–510CrossRefGoogle Scholar
  91. 91.
    Nathavitharana RR, Strnad L, Lederer PA, Shah M, Hurtada RM (2019) Top questions in the diagnosis and treatment of pulmonary M. abscessus disease. Open Forum Infect Dis 6:ofz221. Scholar
  92. 92.
    Koh WJ, Jeon K, Lee NY et al (2011) Clinical significance of differentiation of Mycobacterium massiliense from Mycobacterium abscessus. Am J Respir Crit Care Med 183:405–410PubMedCrossRefGoogle Scholar
  93. 93.
    Choi GE, Shin SJ, Won CJ et al (2012) Macrolide treatment for Mycobacterium abscessus and Mycobacterium massiliense infection and inducible resistance. Am J Respir Crit Care Med 186:917–925PubMedCrossRefGoogle Scholar
  94. 94.
    Park J, Cho J, Lee CH et al (2017) Progression and treatment outcomes of lung disease caused by Mycobacterium abscessus and Mycobacterium massiliense. Clin Infect Dis 64:301–308PubMedCrossRefGoogle Scholar
  95. 95.
    Lee MR, Cheng A, Lee YC et al (2012) CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates. J Antimicrob Chemother 67(1):222–225PubMedCrossRefGoogle Scholar
  96. 96.
    Pryjima M, Burian J, Kuchinski K, Thompson CJ (2017) Antagonism between front-line antibiotics clarithromycin and amikacin in the treatment of Mycobacteria abscessus infections is mediated by the whiB7 gene. Antimicrob Agents Chemother 61:e01353–e01317Google Scholar
  97. 97.
    Martiniano SL, Wagner BD, Levin A, Nick JA, Sagel SD, Daley CL (2017) Safety and effectiveness of clofazimine for primary and refractory nontuberculous mycobacterial infection. Chest 152:800–809PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Ryan K (2018) Mycobacteria abscesus: shapeshifter of the mycobacterial world. Front Microbiol 9:2642. Scholar
  99. 99.
    Ganapathy US, Dartois V, Dick T (2019) Repositioning rifamycins for Mycobacterial abscessus lung disease. Expert Opin Drug Discov 14:869–878. Scholar
  100. 100.
    Philley JV, Wallace RJ Jr, Benwell JL et al (2015) Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease. Chest 48:499–506CrossRefGoogle Scholar
  101. 101.
    Ferro BE, Srivastava S, Deshpande D, Pasipanodya JG, van Soolingen D, Mouton JW, van Ingen J, Gumbo T (2016) Failure of the amikacin, cefoxitin, and clarithromycin combination regimen for treating pulmonary Mycobacterium abscessus infection. Antimicrob Agents Chemother 60:6374–6376PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Pasipanodya JG, Ogbonna D, Ferro BE, Magombedze G, Srivastava S, Deshpande D, Gumbo T (2017) Systematic review and meta-analysis of the effect of chemotherapy on pulmonary Mycobacterium abscessus outcomes and disease recurrence. Antimicrob Agents Chemother 61(11):e01206-17. Scholar
  103. 103.
    Koh WJ, Jeong BH, Kim SY et al (2017) Mycobacterial characteristics and treatment outcomes in Mycobacterium abscessus lung disease. Clin Infect Dis 64:309–316PubMedCrossRefGoogle Scholar
  104. 104.
    Chen J, Zhao L, Mao Y et al (2019) Clinical efficacy and adverse effects of antibiotics used to treat Mycobacterium abscessus pulmonary disease. Front Microbiol 10:1997.
  105. 105.
    Novosad SA, Beekman SWE, Polgreen PM, Macjey K, Winthrop K (2016) M. abscessus study team. Treatment of Mycobacterium abscessus infection. Emerg Infect Dis 22:511–514PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Fukui S, Sekiya N, Takizawa Y et al (2015) Disseminated Mycobacterium abscessus infection following septic arthritis. A case report and review of the literature. Medicine 94(21):e861PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    El Helopu G, Hachem R, viola GM, El Zakhem A, Chaftari AM, Jiang Y, Tarrand J, Raad II (2013) Management of rapidly growing mycobacterial bacteremia in cancer patients. Clin Infect Dis 56:843–846CrossRefGoogle Scholar
  108. 108.
    Lee M-R, Ko J-C, Liang S-K, Lee S-W, Yen DH-T, Hsueh P-R (2014) Bacteremia caused by Mycobacterium abscessus subsp. abscessus and M. abscessus subsp. bolletii: clinical features and susceptibilities of the isolates. Int J Antimicrob Agents 43:438–441PubMedCrossRefGoogle Scholar
  109. 109.
    Jeong SH, Kim S-Y, Huh HJ et al (2017) Mycobacterial characteristics and treatment outcomes in extrapulmonary Mycobacterium abscessus complex infections. Int J Infect Dis 60:49–56PubMedCrossRefGoogle Scholar
  110. 110.
    Tortoli E, Rindi L, Garcia MJ et al (2004) 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 54:1277–1285PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Sax H, Bloemberg G, Hasse B et al (2015) Prolonged outbreak of Mycobacterium chimaera infection after open-chest heart surgery. Clin Infect Dis 61:67–75PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Sommerstein R, Haase B, Marshall J, Sax H, Genoni M, Schegel M, Widner A, the Swiss Chimaera Taskforce (2018) Global health estimate of invasive Mycobacterium chimaera infections associated with heater-cooler devices in cardiac surgery. Emerg Infect Dis 24:576–578PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Schreiber PW, Sax H (2017) Mycobacterium chimaera infections associated with heater-cooler units in cardiac surgery. Curr Opin Infect Dis 30:388–394PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Haller S, Holloer C, Jacobshagen A et al (2016) Contamination during production of heater-cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill 21:30215CrossRefGoogle Scholar
  115. 115.
    Svensson E, Jensen ET, Rasmussen EM, Folkvardsen DR, Norman A, Lillebaek T (2017) Mycobacteria chimaera in heater-cooler units in Denmark related to isolates from the United States and United Kingdom. Emerg Infect Dis 23:507–509PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Marra AR, Diekema DJ, Edmond MB (2017) Mycobacterium chimaera infections associated with contaminated heater-cooler devices for cardiac surgery: outbreak management. Clin Infect Dis 65:669–674PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Chaud M, Lamagni T, Kranzer K et al (2017) Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis 64:335–342CrossRefGoogle Scholar
  118. 118.
    Becker SL, Schotthauser U, Shepherd H-J, Bais R, Trudzinski FC (2019) Epidemiology, clinical presentation, diagnosis and treatment of Mycobacterium chimaera. Pulmonologie 73(08):474–481. [In German with English abstract]. Scholar
  119. 119.
    Scriven JE, Scobie A, Verlander NQ et al (2018) Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect 24(11):1164–1170. Scholar
  120. 120.
    Kasperbauer SH, Daley CL (2019) Mycobacterium chimaera infections related to the heater-cooler unit outbreak: a guide to diagnosis and management. Clin Infect Dis 68:1244–1247PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Zozaya-Valdes E, Porter JL, Coventry J et al (2017) Target specific assay for rapid and quantitative detection of Mycobacterium chimaera DNA. J Clin Microbiol 55:1847–1856PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Nomura J, Rieg G, Bluestone G et al (2019) Rapid detection of invasive Mycobacterium chimaera disease via a novel plasma-based next-generation sequencing test. BMC Infect Dis 19:371PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Mok S, Hannan MM, Nolke L et al (2019) Antimicrobial susceptibility of clinical and environmental Mycobacterium chimaera isolates. Antimicrob Agents Chemother 63:e00755–e00719PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Garvey MI, Ashford R, Bradley CW et al (2016) Decontamination of heater-cooler units associated with contamination by atypical mycobacteria. J Hosp Infect 93:229–234PubMedCrossRefGoogle Scholar
  125. 125.
    Gotting T, Klassen S, Jonas D et al (2016) Heater-cooler units: contamination of crucial devices in cardiothoracic surgery. J Hosp Infect 93:223–228PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • I. W. Fong
    • 1
  1. 1.St. Michael’s HospitalUniversity of TorontoTorontoCanada

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