Key Facts

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause pulmonary disease mimicking TB, particularly in patients with pre-existing lung disease or immunodeficiency. Unlike TB, NTM infections are not transmitted between humans.

Epidemiology

• Incidence increasing worldwide (~5-10 per 100,000 in the UK)
• More common in elderly, COPD, bronchiectasis, cystic fibrosis, and post-menopausal women
• HIV with CD4 <50: disseminated MAC is an AIDS-defining illness
• Geography: M. kansasii more common in urban areas; M. xenopi in Southern England

Aetiology

• Environmental organisms found in soil, water (including domestic water supplies), and biofilms
• Slow-growing: MAC (M. avium, M. intracellulare), M. kansasii, M. xenopi, M. malmoense
• Rapid-growing: M. abscessus complex, M. chelonae, M. fortuitum
• Not transmitted person-to-person (except possibly M. abscessus in CF patients)

Pathophysiology

• Inhalation of environmental NTM or aspiration from colonised water sources
• Host susceptibility is key — NTM is rarely pathogenic in healthy lungs
• Pre-existing structural lung disease (bronchiectasis, cavities, bullae) provides environment for colonisation
• Impaired mucociliary clearance and immune dysfunction allow progressive infection
• Granuloma formation similar to TB but often non-caseating

Pulmonary NTM Disease

Cavitatory form (fibrocavitatory):

• Predominantly in older men with COPD/smoking history
• Upper lobe cavitation mimicking TB
• Cough, haemoptysis, weight loss

Nodular/bronchiectatic form (Lady Windermere syndrome):

• Predominantly in elderly women without traditional risk factors
• Middle lobe/lingula bronchiectasis with centrilobular nodules
• Chronic cough, often attributed to bronchiectasis

Disseminated NTM (HIV/AIDS)

• CD4 <50 cells/µL
• Fever, weight loss, night sweats
• Hepatosplenomegaly, lymphadenopathy
• Pancytopenia, markedly raised ALP

Other NTM Manifestations

• Skin/soft tissue: M. marinum (swimming pool/fish tank granuloma), M. chelonae, M. abscessus
• Lymphadenitis: typically cervical, children (MAC)

Red Flags

• Positive AFB smear in non-TB patient
• Persistent cavitation despite TB treatment
• Worsening bronchiectasis despite standard management
• M. abscessus in CF patient (may preclude transplant)

Bedside

• Sputum samples: 3 early morning sputum for AFB smear and mycobacterial culture

Bloods

• FBC: anaemia, lymphopenia (HIV)
• LFTs: baseline before treatment
• HIV test: all patients with NTM
• ESR/CRP: inflammatory markers

Imaging

• HRCT: cavitation (fibrocavitatory), middle lobe/lingula bronchiectasis with centrilobular nodules (nodular-bronchiectatic), tree-in-bud pattern
• CXR: may show cavitation, infiltrates, nodules

Special Tests

• Mycobacterial culture (Lowenstein-Jensen/BACTEC): gold standard; species identification; takes 2-8 weeks
• ATS/IDSA diagnostic criteria (all 3 required):
  1. Clinical: compatible symptoms + exclusion of other diagnoses
  2. Radiological: nodular/cavitatory opacities on CXR OR HRCT showing bronchiectasis + nodules
  3. Microbiological: ≥2 positive sputum cultures, OR 1 positive BAL culture, OR biopsy with granulomas + positive culture
• Drug susceptibility testing: essential, especially for M. abscessus (clarithromycin resistance)
• Bronchoscopy with BAL: if unable to produce sputum
• CT-guided biopsy: if tissue diagnosis needed

Non-pharmacological

• Specialist decision to treat: not all NTM isolates require treatment; weigh risks vs benefits
• Address underlying conditions (optimise bronchiectasis, COPD, CF management)
• Airway clearance techniques
• Nutritional support

Pharmacological

BTS Guidelines — species-specific:

MAC (M. avium complex):

• Rifampicin 600mg OD + ethambutol 15mg/kg OD + clarithromycin 500mg BD (or azithromycin 250mg OD)
• Treat for 12 months after sputum culture conversion
• Severe/cavitatory: consider adding amikacin IV/nebulised for initial 1-3 months

M. kansasii:

• Rifampicin 600mg OD + ethambutol 15mg/kg OD + isoniazid 300mg OD (+ pyridoxine)
• Duration: 12 months after culture conversion

M. abscessus complex:

• Most challenging to treat; often requires IV induction + oral maintenance
• IV induction (~1-3 months): amikacin 15mg/kg OD + tigecycline 50mg BD + imipenem 1g BD (or cefoxitin)
• Oral maintenance: clarithromycin 500mg BD (if susceptible) + 1-2 additional agents (clofazimine, linezolid)
• Duration: prolonged (12-24 months); often incurable

M. malmoense:

• Rifampicin + ethambutol + clarithromycin for ≥12 months after conversion

M. xenopi:

• Rifampicin + ethambutol + clarithromycin ± isoniazid or fluoroquinolone for ≥12 months after conversion

Surgical/Interventional

• Surgical resection (lobectomy): considered for localised disease, particularly M. abscessus, if medical therapy failing
• Adjunctive to medical therapy rather than standalone

Referral Criteria

• All suspected NTM disease should be managed by or in consultation with a specialist in NTM/mycobacterial disease
• CF patients with NTM: joint respiratory/CF/ID management
• Pre-transplant M. abscessus: specialist transplant centre assessment

• MAC pulmonary disease: culture conversion achieved in ~50-70% with appropriate therapy
• M. kansasii: best outcomes; cure rate ~90% with rifampicin-based regimen
• M. abscessus: worst prognosis; cure rates <50%; often chronic/suppressive therapy
• Cavitatory disease has worse outcomes than nodular-bronchiectatic
• Relapse rate: ~10-20% after treatment completion
• Disseminated MAC in HIV: excellent response to ART + antimycobacterial therapy
• NTM pulmonary disease associated with increased all-cause mortality vs matched controls

NTM Treatment Summary

ATS/IDSA Diagnostic Criteria