Microbiology of NTM Pulmonary Disease

NTM are members of the genus Mycobacterium excluding M. tuberculosis complex and M. leprae, the causative agents of tuberculosis and leprosy respectively. NTM are commonly divided into rapid and slow growing subgroups:1,4  

 

  • Rapidly growing NTM form colonies within 7 days
  • Slowly growing NTM require over 7 days, and sometimes up to 12 weeks, to form colonies

 

This phenotypic division remains clinically relevant, as important differences in management exist between the two groups.1  
 

Mycobacteria and NTM Species Overview4,5

 

NTM Microbiology Species overview

Geographic Distribution of NTM Pulmonary Disease

 

The distribution of NTM species causing pulmonary disease varies by geographic region.3 M. avium complex (MAC) and M. abscessus are responsible for the bulk of NTM pulmonary disease in the US, making up approximately 80.1% and 12.1% of cases, respectively.2 A survey on diagnostic and treatment practices for NTM pulmonary disease in five European countries (France, Germany, Italy, Spain and the UK) and Japan found that MAC predominated as the causative agent of NTM pulmonary disease (Europe: 79.4%; Japan: 85.1%), followed by M. abscessus (Europe: 20%; Japan: 14.9%).6

Distribution of NTM Species Causing Pulmonary Disease by Country2,6,7

 

NTM Microbiology NTM species

NR, not reported

Mycobacterium avium Complex 

MAC, which consists of several closely related slowly growing species, is the most common cause of NTM pulmonary disease worldwide. Within the complex, M. avium, M. intracellulare, and M. chimaera are the most common human pathogens.8 

M. avium Complex

 

NTM microbiology M. avium

Mycobacterium abscessus 

M. abscessus is the most common rapidly growing species responsible for causing NTM pulmonary disease. The taxonomy of M. abscessus has evolved, but it currently comprises three closely related subspecies—abscessus, massiliense, and bolletii.9

M. abscessus is Comprised of Three Closely Related Subspecies9

NTM Microbiology M. abscessus

Subspecies abscessus is the most common – 61.3% (n=1,344) of clinical isolates were identified as subspecies abscessus in a large surveillance study including 2,191 isolates from the US. In the same case series, 34.4% (n=754) of isolates were subspecies massiliense and 4.2% (n=93) of isolates were subspecies bolletii.10  Similar data from Japan (n=321) reported a similar distribution with 57.0% (n=183) of M. abscessus isolates being subspecies abscessus while 41.4% (n=133) were subspecies massiliense and 1.6% (n=5) were subspecies bolletii.11 Subspecies bolletii is uncommon in North America and Asia,10,12 but accounts for approximately 15% of all M. abscessus isolates in studies from Europe.12-14  

Learn about the pathogenesis of NTM pulmonary disease

References

  1. Cowman S, van Ingen J, Griffith DE, Loebinger MR. Non-tuberculous mycobacterial pulmonary disease. Eur Respir J. 2019;54(1)doi:10.1183/13993003.00250–2019
  2. 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(7):970-6. doi:10.1164/rccm.201002–0310OC
  3. Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med. 2015;36(1):13-34. doi:10.1016/j.ccm.2014.10.002
  4. Mickymaray S, Alfaiz FA, Paramasivam A. Efficacy and Mechanisms of Flavonoids against the Emerging Opportunistic Nontuberculous Mycobacteria. Antibiotics (Basel). 2020;9(8)doi:10.3390/antibiotics9080450
  5. Johansen MD, Herrmann JL, Kremer L. Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus. Nat Rev Microbiol. 2020;18(7):392–407. doi:10.1038/s41579-020-0331-1
  6. van Ingen J, Wagner D, Gallagher J, et al. Poor adherence to management guidelines in nontuberculous mycobacterial pulmonary diseases. Eur Respir J. 2017;49(2)doi:10.1183/13993003.01855-2016
  7. Namkoong H, Kurashima A, Morimoto K, et al. Epidemiology of Pulmonary Nontuberculous Mycobacterial Disease, Japan. Emerg Infect Dis. 2016;22(6):1116–7. doi:10.3201/eid2206.151086
  8. Daley CL. Mycobacterium avium Complex Disease. Microbiol Spectr. 2017;5(2)doi:10.1128/microbiolspec.TNMI7-0045-2017
  9. Lee MR, Sheng WH, Hung CC, Yu CJ, Lee LN, Hsueh PR. Mycobacterium abscessus Complex Infections in Humans. Emerg Infect Dis. 2015;21(9):1638-46. doi:10.3201/2109.141634
  10. Hunkins JJ, de-Moura VC, Eddy JJ, Daley CL, Khare R. In vitro susceptibility patterns for rapidly growing nontuberculous mycobacteria in the United States. Diagn Microbiol Infect Dis. 2023;105(3):115882. doi:10.1016/j.diagmicrobio.2022.115882
  11. Kamada K, Yoshida A, Iguchi S, et al. Nationwide surveillance of antimicrobial susceptibility of 509 rapidly growing mycobacteria strains isolated from clinical specimens in Japan. Sci Rep. 2021;11(1):12208. doi:10.1038/s41598-021-91757-4
  12. Ruedas-López A, Tato M, Broncano-Lavado A, et al. Subspecies Distribution and Antimicrobial Susceptibility Testing of Mycobacterium abscessus Clinical Isolates in Madrid, Spain: a Retrospective Multicenter Study. Microbiol Spectr. 2023;11(3):e0504122. doi:10.1128/spectrum.05041–22
  13. Mougari F, Amarsy R, Veziris N, et al. Standardized interpretation of antibiotic susceptibility testing and resistance genotyping for Mycobacterium abscessus with regard to subspecies and erm41 sequevar. J Antimicrob Chemother. 2016;71(8):2208–12. doi:10.1093/jac/dkw130
  14. Teri A, Sottotetti S, Arghittu M, et al. Molecular characterization of Mycobacterium abscessus subspecies isolated from patients attending an Italian Cystic Fibrosis Centre. New Microbiol. 2020;43(3):127–132. 
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