321.1 🎓 醫孞生版

321.1.0.1 📌 䞀頁重點

321.1.0.1.1 Overview
321.1.0.1.1.1 NTM (Non-Tuberculous Mycobacteria)
  • 200+ species
  • Ubiquitous in environment (water, soil)
  • Transmission: environmental exposure (not person-to-person typically)
  • Causes pulmonary + extrapulmonary disease (skin, lymph, disseminated)
321.1.0.1.1.2 Pulmonary NTM Pathogens (Major)
  • M. avium complex (MAC) — most common
    • M. avium
    • M. intracellulare
    • M. chimaera
  • M. abscessus complex (MABC) — most difficult to treat
    • M. abscessus subsp. abscessus
    • M. abscessus subsp. massiliense
    • M. abscessus subsp. bolletii
  • M. kansasii — TB-like
  • M. xenopi — Europe
  • M. malmoense — Europe
  • M. simiae
  • M. fortuitum complex (less pulmonary)
  • M. chelonae (less pulmonary)
321.1.0.1.2 Epidemiology
  • Incidence rising globally (HRCT availability, aging, immunosuppression)
  • NTM prevalence in some areas now > TB
  • Pulmonary > extrapulmonary
  • Women > men in MAC (especially thin postmenopausal)
  • Environmental sources:
    • Showerheads (MAC)
    • Hot tubs (MAC — hot tub lung)
    • Soil (M. kansasii, M. fortuitum)
    • Healthcare contamination (M. chimaera from cardiac heater-cooler units 2014 outbreak)
321.1.0.1.3 Risk Factors

321.1.1 Patient Factors

  • Bronchiectasis (any cause — CF, post-infectious, primary ciliary dyskinesia)
  • COPD
  • Prior TB (residual structural damage)
  • Aspergillosis (ABPA)
  • Sarcoidosis
  • Cystic fibrosis (esp M. abscessus)
  • Hot tub use (MAC)
  • GERD
  • Female, postmenopausal, thin
  • Pectus excavatum
  • Mitral valve prolapse
  • Immunosuppression:
    • HIV (esp MAC disseminated when CD4 < 50)
    • TNF-α inhibitors
    • Solid organ transplant
    • Hematopoietic stem cell transplant
    • Long-term steroids
  • Genetic:
    • IFN-γ receptor deficiency
    • IL-12 receptor deficiency
    • GATA2 deficiency
321.1.1.0.1 Clinical Presentation

321.1.2 Pulmonary NTM Disease Types

Nodular Bronchiectatic Disease: - “Lady Windermere syndrome” (MAC most common) - Tall thin elderly women - Right middle lobe + lingula bronchiectasis - Tree-in-bud nodules - Cough, mild constitutional symptoms - Slow progression

Fibrocavitary Disease: - Upper lobe cavities (TB-like) - More aggressive - Mostly in patients with underlying lung disease (COPD, post-TB) - Common with M. kansasii

Hypersensitivity-Like Pneumonitis (Hot Tub Lung): - MAC inhalation from hot tubs - Immune-mediated rather than infection alone - Constitutional + diffuse infiltrates

Disseminated: - HIV with CD4 < 50 - MAC bacteremia - Multi-organ involvement - Treatment: macrolide + ethambutol + rifabutin

321.1.3 Symptoms

  • Chronic cough
  • Sputum production
  • Fatigue
  • Weight loss
  • Hemoptysis (less common than TB)
  • Fever (less common)
  • Often insidious
321.1.3.0.1 Diagnosis — ATS/IDSA 2020 Criteria

Clinical Criteria (ALL of): - Pulmonary symptoms (chronic cough, sputum, dyspnea, etc.) - Nodular or cavitary opacities on CXR OR bronchiectasis + multiple small nodules on HRCT - Exclusion of other diagnoses

Microbiologic Criteria (ANY of): - ≥ 2 positive sputum cultures for same NTM species (separate samples) - ≥ 1 positive BAL or bronchial wash for NTM - Lung biopsy with mycobacterial histopathology (granulomatous inflammation + AFB+ on culture/PCR)

321.1.3.0.1.1 Workup
  • Sputum AFB smear + culture + identification (DNA probe, MALDI-TOF)
  • Drug susceptibility testing (macrolide-resistant MAC particularly important)
  • HRCT chest
  • HIV testing (if MAC and risk)
  • Immunoglobulin levels (CVID)
  • CFTR (if suspicion)
  • Ciliary studies (if suspicion of PCD)
321.1.3.0.2 Treatment
321.1.3.0.2.1 MAC Pulmonary Disease (Most Common)

Standard Regimen: - Macrolide (azithromycin 250-500 mg daily OR thrice weekly) - Ethambutol 15 mg/kg daily - Rifampin 10 mg/kg daily

Duration: 12 months after sputum culture conversion - Total often 18-24 months - 3 negative monthly cultures = conversion

Thrice-Weekly Regimen (for nodular bronchiectatic, less severe): - Azithromycin 500 mg + ethambutol 25 mg/kg + rifampin 600 mg, 3x/week - Less toxicity - Comparable efficacy

Daily Regimen (cavitary, severe): - Azithromycin 250 mg + ethambutol 15 mg/kg + rifampin 10 mg/kg daily

Macrolide-Resistant MAC: - Treat without macrolide → poor outcomes - Consider surgery if possible - ALIS for refractory

Inhaled Amikacin (Liposomal — ALIS / Arikayce): - CONVERT trial 2018: ↑ culture conversion in refractory MAC - FDA 2018 approved for refractory MAC pulmonary disease (failed standard ≥ 6 months) - 590 mg inhaled daily - Side effects: dysphonia, cough

321.1.3.0.2.2 M. abscessus Complex (MABC) — Difficult

Components: - M. abscessus subsp. abscessus: erm(41) gene → macrolide resistance (inducible) - M. abscessus subsp. massiliense: erm(41) inactive → macrolide-susceptible - M. abscessus subsp. bolletii: variable

Treatment: - Intensive Phase (IV, 2-3 months): - Amikacin IV + Imipenem-cilastatin or cefoxitin + Macrolide (if susceptible) + Tigecycline or eravacycline or linezolid

  • Continuation Phase (PO):
    • Macrolide (if susceptible) + Clofazimine + Bedaquiline (emerging) + others

Duration: ≥ 12 months after culture conversion; often lifelong suppression

Outcomes: Cure rates 30-50%; high relapse

Newer Agents: - Bedaquiline: ATP synthase inhibitor; used in MABC - Clofazimine: anti-mycobacterial - Tedizolid: alternative to linezolid

321.1.3.0.2.3 M. kansasii

Treatment: - Rifampin + Isoniazid + Ethambutol (similar to TB) - ± Macrolide (azithromycin) - Duration: 9-12 months - More TB-like, often curable

321.1.3.0.2.4 M. xenopi, M. malmoense
  • Macrolide + ethambutol + rifampin
  • M. xenopi: macrolide + ethambutol + rifampin + moxifloxacin (severe)
  • M. malmoense: macrolide + ethambutol + rifampin
321.1.3.0.2.5 Disseminated MAC (HIV with CD4 < 50)
  • Macrolide (clarithromycin or azithromycin) + ethambutol + rifabutin (less drug interaction with HIV)
  • ART critical
  • Prophylaxis with azithromycin if CD4 < 50
321.1.3.0.3 Surgical Resection
321.1.3.0.3.1 Indications
  • Localized disease
  • Drug-resistant (esp M. abscessus)
  • Cavitary disease not responding
  • Hemoptysis
  • Aspergilloma in NTM cavity
321.1.3.0.3.2 Outcomes
  • Often beneficial as adjunct
  • Combined with multidrug therapy
  • Selected patients
321.1.3.0.4 Special Topics
321.1.3.0.4.1 Hot Tub Lung (MAC)
  • Inhalation of aerosolized MAC
  • Hypersensitivity-like reaction
  • Diffuse pulmonary infiltrates
  • Avoid hot tub
  • Drainage + cleaning hot tub
  • Steroids + antimicrobial in some
321.1.3.0.4.2 M. chimaera Cardiac Surgery Outbreak (2014)
  • Heater-cooler units contaminated
  • Disseminated infection post-cardiac surgery
  • Long incubation (months-years)
  • Treatment: prolonged combination antibiotics
321.1.3.0.4.3 Cystic Fibrosis + M. abscessus
  • Devastating in CF
  • May exclude from lung transplant
  • Aggressive multi-drug therapy
  • Inhaled antibiotics often included
321.1.3.0.4.4 MAC + Immune Disorders
  • GATA2 deficiency: disseminated NTM + warts + AML
  • IFN-γ pathway defects
  • Specialized immunology eval
321.1.3.0.5 Public Health
  • NTM not reportable in most countries
  • Not transmitted person-to-person (unlike TB)
  • Source control challenging (environmental)

321.1.3.1 🩺 床邊速查

  • MAC most common pulmonary NTM
  • M. abscessus most difficult to treat
  • Lady Windermere: tall thin elderly women + RML/lingula bronchiectasis + MAC
  • Diagnosis (ATS/IDSA 2020): clinical + radiographic + microbiologic (2 sputum or 1 BAL or 1 tissue)
  • MAC treatment: azithromycin + ethambutol + rifampin × 12 months after culture conversion
  • MAC refractory: add ALIS (inhaled liposomal amikacin) — CONVERT 2018
  • M. abscessus: multi-drug IV + PO ≥ 12 months; cure rates 30-50%
  • M. kansasii: rifampin + isoniazid + ethambutol × 9-12 months (TB-like)
  • Disseminated MAC in HIV: CD4 < 50; prophylaxis with azithromycin