Microbiology & infectious diseases

Mycobacteria

Mycobacteria non-TB


Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Ateeqa Mujeeb Ullah, M.D.
Lili Lee, M.D.

Last author update: 30 August 2022
Last staff update: 6 December 2023

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PubMed Search: Mycobacteria other than tuberculosis

Ateeqa Mujeeb Ullah, M.D.
Lili Lee, M.D.
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Cite this page: Ullah AM, Lee L. Mycobacteria non-TB. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/microbiologymyconontb.html. Accessed March 29th, 2024.
Definition / general
  • Mycobacteria other than Mycobacterium tuberculosis (MTB) and Mycobacterium leprae
  • Other terminologies: atypical mycobacteria, mycobacteria other than tuberculosis (MOTT)
  • Gram positive, catalase positive, acid fast, rod shaped, aerobic, slow growing bacteria
Essential features
  • Low virulence ubiquitous organisms affecting mostly patients with pre-existing lung disease or immunosuppression
  • Different species need specific environments and time periods for optimal growth
  • Culture is the gold standard for diagnosis; however, it cannot differentiate Mycobacterium tuberculosis from nontuberculous mycobacteria or its different subspecies
  • Mycobacterium abscessus complex (MABC) has poor prognosis due to resistance to antibiotics
Epidemiology
  • Generally low virulence but incidence of MOTT related lung disease increasing globally, especially in tropical weather (Front Immunol 2020;11:303)
  • Ubiquitous organisms / environmental bacteria found in water, soil, dust and vegetation
  • Infrequent person to person transmission, except with M. abscessus that has been discovered among cystic fibrosis patients (Indian J Med Res 2020;152:185)
  • Commonly affects elderly people with pre-existing lung disease (Microbiol Spectr 2017;5)
  • Mycobacterium avium complex (MAC) is the most common species found in most areas, followed by M. abscessus complex and Mycobacterium kansasii, although variance occurs based on geography (Eur Respir J 2013;42:1604)
Sites
  • Lung, most commonly involved organ (65 - 90%) (Adv Exp Med Biol 2017;944:19)
  • Other sites that can be affected include lymph nodes, skin, soft tissues and rarely bones
  • Disseminated nontuberculous mycobacterial disease is rare and occurs in individuals with congenital or acquired immune defects such as HIV / AIDS (Indian J Med Res 2020;152:185)
Pathophysiology
Clinical features
  • Most commonly involves the lung, followed by skin and soft tissue (following surgery or trauma), local device associated infection (e.g., central line), lymph nodes and blood (disseminated in immunosuppressed patients) (CDC: Nontuberculous Mycobacteria (NTM) Infections [Accessed 26 August 2022])
  • Skin disorders (ulcerations, abscesses, rheumatoid-like nodules, histiocytic reactions, panniculitis), most commonly due to M. kansasii, M. marinum, M. ulcerans
  • Lung manifestations: fibrocavitary disease, nodular bronchiectasis and hypersensitivity pneumonitis (Front Immunol 2020;11:303)
  • Challenging to diagnose due to overlapping symptomatology with underlying lung disease and slow growth in culture
  • Difficult to treat due to drug resistance
Diagnosis
  • Nontuberculous mycobacteria exist naturally in the environment; therefore, isolation from a nonsterile respiratory specimen does not mean they are causative organisms of lung disease, which makes the diagnosis very challenging (Eur Respir J 2013;42:1604)
  • The approach includes the integration of clinical, radiographic and microbiological data (with the latter being the gold standard) and including:
    • At least 2 positive sputum cultures
    • 1 positive culture in the case of bronchoscopic wash or lavage, or
    • Transbronchial or other lung biopsy with a positive culture for nontuberculous mycobacteria or compatible histopathological features such as granulomatous inflammation or stainable acid fast bacilli (AFB) and 1 positive sputum or bronchial wash culture for nontuberculous mycobacteria, regardless of the mycobacterial strain (Am J Respir Crit Care Med 2007;175:367)
  • Latest approaches in diagnosis include molecular methods such as line probe hybridization, polymerase chain reaction (PCR) restriction fragment length polymorphism analysis, real time PCR and DNA sequencing
  • Most accurate detection method includes gene sequencing; however, it is very cumbersome, expensive and not readily available (Tuberc Respir Dis (Seoul) 2016;79:74)
Laboratory
  • Nontuberculous mycobacteria can be cultured on:
    • Solid growth media including Löwenstein-Jensen agar, Middlebrook 7H10 and 7H11 media
    • Liquid media containing enriched Middlebrook 7H9 broth is more sensitive but prone to contamination (Tuberc Respir Dis (Seoul) 2016;79:74)
  • Colonies on solid media differ for different subspecies (e.g., M. kansasii gives bright yellow colonies after exposure to light)
Radiology images

Images hosted on other servers:
Missing Image

Jejunal loops and extensive lymphadenopathy (MAI)

Case reports
Treatment
  • Amikacin is an effective drug against most nontuberculous mycobacterial species
  • Macrolides (clarithromycin and azithromycin) are the cornerstones of treatment for Mycobacterium avium complex lung disease (Clin Chest Med 2015;36:55)
  • M. kansasii is easily treatable with sensitivity to standard anti-TB drugs, except for pyrazinamide (Future Microbiol 2014;9:1095)
  • M. abscessus complex has poor outcomes due to its resistance to most known treatment modalities (Clin Chest Med 2015;36:67)
  • Except for M. kansasii, nontuberculous mycobacterial lung disease is difficult to control with antimicrobial therapy alone and may require surgical intervention; however, the role of adjunct surgical approaches remains unclear
  • Current guidelines recommend that medical therapy should be continued until the patient has sputum cultures that are persistently negative for 12 months while undergoing treatments, including surgery (Tuberc Respir Dis (Seoul) 2016;79:74)
Clinical images

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Bright yellow colonies Bright yellow colonies

Bright yellow colonies

Swimming pool granuloma

Swollen, red papules and nodules


Ulcer on the lateral surface of the fifth toe

Gross description
Microscopic (histologic) description
  • M. tuberculosis and nontuberculous mycobacteria may share the same spectrum of histological findings; therefore, no reliable differentiation between them can be made microscopically (Semin Diagn Pathol 2017;34:518)
  • Typically phagocytosed by foamy histiocytes that may form necrotizing or nonnecrotizing granulomas
  • AIDS patients: histiocytes may contain abundant acid fast organisms; may lack well formed granulomata and lymphocytic response
Microscopic (histologic) images

Contributed by Chaohui L. Zhao, M.D. and Vicente Nazareno
Granulomatous inflammation Granulomatous inflammation Granulomatous inflammation

Granulomatous inflammation

Pink slender rods

Pink slender rods

Pink-red slender rods

Pink-red slender rods

Yellow-green fluorescent rods

Yellow-green fluorescent rods

Positive stains
Videos

Quick revision of nontuberculous mycobacteria with mnemonics

Differential diagnosis
Board review style question #1
Which of the following is the common setting of person to person transmission of a nontuberculous Mycobacterium species?

  1. Mycobacterium abscessus in cystic fibrosis patients
  2. Mycobacterium gordonae in HIV patients
  3. Mycobacterium kansasii in organ transplant patients
  4. Mycobacterium mucogenicum in patients on chemotherapy
  5. Mycobacterium scrofulaceum in individuals > 90 years old
Board review style answer #1
A. Mycobacterium abscessus in cystic fibrosis patients

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Reference: Mycobacteria non-TB
Board review style question #2

A thin, immunocompetent 80 year old man presents with chronic obstructive pulmonary disease and a chronic cough. Sputum smears were acid fast positive, with colorless colonies that grew from multiple specimens after culture at 32 °C and turned yellow after exposure to light. Which of the following is the most likely etiologic agent causing his infection?

  1. Mycobacterium abscessus
  2. Mycobacterium avium complex
  3. Mycobacterium gordonae
  4. Mycobacterium kansasii
  5. Mycobacterium scrofulaceum
Board review style answer #2
D. Mycobacterium kansasii

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Reference: Mycobacteria non-TB
Board review style question #3
The most reliable method to differentiate M. tuberculosis from nontuberculous mycobacteria is

  1. Culture on liquid media
  2. Gene sequencing
  3. Histology
  4. Immunohistochemical or special stains
  5. PCR based assays
Board review style answer #3
B. Gene sequencing

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Reference: Mycobacteria non-TB
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