000 Non Tuberculous Mycobacterium (NTM MAI MAC)

    • Nontuberculous Mycobacteria (NTM), Mycobacterium Avium-Intracellulare (MAI), and Mycobacterium Avium Complex (MAC)

      • Etymology:
        • Nontuberculous Mycobacteria (NTM): “Non-tuberculous” describes mycobacteria other than Mycobacterium tuberculosis (including bovine TB) and Mycobacterium leprae.
        • Mycobacterium Avium-Intracellulare (MAI): Named after Mycobacterium avium and Mycobacterium intracellulare, which were historically described as separate species.
        • Mycobacterium Avium Complex (MAC): Describes the closely related species M. avium and M. intracellulare grouped due to similar clinical behavior.
      • AKA:
        • NTM
        • MAC
        • MAI
        • Atypical Mycobacterial Infection
        • Environmental Mycobacteria
      • What is it?
        • Nontuberculous mycobacteria (NTM) are a diverse group of mycobacteria distinct from Mycobacterium tuberculosis (including bovine TB) and Mycobacterium leprae.
        • The most common pathogens within this group are Mycobacterium avium and Mycobacterium intracellulare, often grouped as Mycobacterium Avium Complex (MAC).
        • Opportunistic pathogens causing pulmonary and disseminated infections, especially in immunocompromised patients.
      • Caused by:
        • Inhalation or ingestion of environmental mycobacteria.
        • Exposure to soil, water, and aerosolized biofilms.
        • More common in immunocompromised hosts, such as those with HIV/AIDS or structural lung disease (e.g., bronchiectasis, COPD).
      • Resulting in:
        • Chronic lung infections.
        • Disseminated infections in immunocompromised patients.
        • Hypersensitivity pneumonitis (e.g., hot tub lung).
      • Structural Changes:
        • Bronchiectasis
        • Cavitation and fibrosis (less common than in MTB but possible)
        • Centrilobular nodules
        • Tree-in-bud opacities
      • Pathophysiology:
        • MAC organisms resist immune clearance, leading to granulomatous inflammation.
        • May persist in macrophages, causing chronic infection.
      • Pathology:
        • Granulomatous inflammation
        • Non-caseating granulomas (contrast to Mycobacterium tuberculosis)
        • Acid-fast bacilli (AFB) on staining
      • Diagnosis:
        • Clinical symptoms + Imaging findings + Microbiological confirmation
        • Positive sputum cultures (multiple specimens recommended)
        • Bronchoalveolar lavage in non-productive cough cases
        • AFB smear and Mycobacterial culture
        • NAAT and PCR for confirmation
      • Clinical:
        • Chronic cough with or without sputum production
        • Fatigue, weight loss, night sweats
        • Dyspnea
        • Hemoptysis in advanced disease
        • Disseminated MAC: fever, hepatosplenomegaly, lymphadenopathy (HIV/AIDS)
      • Radiology:
        • CXR:
          • Nodular opacities, especially middle lobe and lingula
          • Tree-in-bud opacities
          • Bronchiectasis and consolidation in advanced disease
        • CT:
          • Parts: Lungs, middle lobe and lingula
          • Size: Diffuse nodular disease, small centrilobular nodules
          • Shape: Nodular with tree-in-bud appearance
          • Position: Bilateral, often upper and middle lobes
          • Character: Cavitation less common than tuberculosis but possible
          • Time: Chronic progression over months to years
        • MRI/PET CT/NM/US/Angio:
          • Rarely used for pulmonary cases, may show lymphadenopathy in disseminated disease
      • Labs:
        • Positive AFB smear and culture
        • Elevated inflammatory markers (CRP, ESR)
        • NAAT testing for species confirmation
      • Management:
        • Antibiotic therapy with a macrolide-based regimen:
          • Clarithromycin or azithromycin
          • Rifampin or rifabutin
          • Ethambutol
        • Treatment duration: Minimum 12 months after culture conversion
        • Surgery may be considered for localized cavitary disease
      • Radiology Detail:
        • CXR: Nodular opacities, bronchiectasis, and tree-in-bud pattern
        • CT: Bronchiectasis, small centrilobular nodules, cavitation, and tree-in-bud pattern
        • MRI/PET: Limited role, mainly for complications
      • Pulmonary Function Tests (PFTs):
        • May show obstructive or mixed obstructive-restrictive patterns
      • Recommendations:
        • Confirm diagnosis with microbiological criteria
        • Consider underlying immunodeficiency testing
        • Prolonged multidrug therapy
      • Key Points and Pearls:
        • MAC is a key cause of chronic pulmonary infections in non-smoking elderly women with bronchiectasis.
        • Not all positive MAC cultures indicate active disease; clinical correlation is essential.
        • Tree-in-bud nodularity is a hallmark finding.
        • Disseminated MAC is a major concern in AIDS patients with CD4 <50.
      • Citations:
        • Griffith DE, Aksamit T, Brown-Elliott BA et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175(4):367-416.
        • Sharma SK, Mohan A. Mycobacterium avium complex disease: Pulmonary and disseminated forms. Indian J Med Res. 2015;141(1):56-70.
        • Stout JE, Koh WJ, Yew WW. Update on pulmonary disease due to non-tuberculous mycobacteria. Int J Infect Dis. 2016;45(1):123-134.
    Feature Mycobacterium tuberculosis (MTB) Atypical Mycobacterium (NTM- Non Tuberculous Mycobacteria)  

    eg avium-intracellulare (MAC)
    Pathogen Type Mycobacterium tuberculosis complex (MTB) Mycobacterium avium and Mycobacterium intracellulare
    Transmission Human-to-human via airborne droplets Environmental exposure (soil, water, aerosols)
    Primary Reservoir Humans Environment (soil, water, birds, animals)
    Virulence and Pathogenicity Highly virulent, infects healthy individuals Opportunistic, primarily affects immunocompromised patients (HIV/AIDS)
    Primary Affected Population General population, especially in endemic areas Immunocompromised patients (e.g., HIV/AIDS, elderly with structural lung disease)
    Clinical Presentation Fever, night sweats, cough, hemoptysis, weight loss Chronic cough, fatigue, weight loss, occasional hemoptysis
    Pulmonary Involvement Cavitary lesions, consolidation, apical nodules Bronchiectasis, nodular opacities, tree-in-bud pattern
    CXR Features Upper lobe cavitation, consolidation, nodules, apical fibrosis Middle lobe and lingula involvement, nodular opacities, tree-in-bud pattern
    CT Features – Upper lobe predominant cavitation, apical scarring, tree-in-bud opacities
    – Patchy consolidation, centrilobular nodules    		 – Middle lobe and lingula nodular opacities
    – Bronchiectasis with mucus plugging
    – Tree-in-bud nodularity
    Extrapulmonary Involvement Common (e.g., lymph nodes, CNS, bones, GI tract) Rare, mainly disseminated in immunocompromised hosts
    Histopathology Caseating granulomas, Langhans giant cells Non-caseating granulomas or granuloma absence
    Diagnosis Sputum AFB smear, culture, PCR (GeneXpert) Sputum culture, PCR, MAC-specific NAAT
    Infectiousness Highly contagious Not contagious between humans
    Drug Susceptibility Requires prolonged treatment, MDR strains exist Less drug resistance compared to MTB
    First-line Treatment Isoniazid (INH), Rifampin (RIF), Pyrazinamide (PZA), Ethambutol (EMB) Clarithromycin or Azithromycin + Ethambutol, Rifabutin
    Treatment Duration 6-9 months (18 months for MDR-TB) 12-18 months or until culture negative for 12 months
    Prevention BCG vaccination, infection control measures Avoidance of environmental exposure (e.g., contaminated water)
    Geographical Distribution Endemic in developing countries Worldwide, especially in immunocompromised patients
    Complications Miliary TB, tuberculomas, Pott’s disease Disseminated disease in AIDS, MAC lung disease
    Immune Response Delayed-type hypersensitivity (DTH), granuloma formation Weak immune response, especially in immunocompromised