321.3 🏥 內科專科考前版

321.3.1 Mechanistic Deep Dive

321.3.1.1 Macrolide Resistance in NTM

  • MAC: rrl 23S rRNA gene mutations
  • M. abscessus: erm(41) inducible (subsp. abscessus, bolletii); rrl mutations also possible
  • Distinguish macrolide-susceptible (M. massiliense) vs resistant (M. abscessus) — affects outcome

321.3.1.2 Drug Mechanisms in NTM

  • Macrolides: 50S ribosome
  • Ethambutol: arabinogalactan (cell wall)
  • Rifampin: RNA polymerase
  • Amikacin: 30S ribosome
  • Bedaquiline: ATP synthase
  • Clofazimine: cell membrane disruption + oxidative damage

321.3.2 Recent Trials & Updates

321.3.2.1 CONVERT (2018) — ALIS for Refractory MAC

  • N = 336 MAC pulmonary disease + macrolide-containing regimen ≥ 6 mo
  • ALIS + standard vs standard alone
  • ↑ Culture conversion 29% vs 9%
  • FDA 2018 approval
  • Practice-changing

321.3.2.2 COVID-19 + NTM

  • Long-term lung damage may predispose
  • Surveillance after severe COVID-19

321.3.2.3 Bedaquiline in M. abscessus

  • Limited data
  • Compassionate use
  • Phase 2 trials ongoing

321.3.2.4 Omadacycline for NTM

  • Tetracycline-class
  • Approved for community-acquired bacterial pneumonia + ABSSSI
  • Off-label for M. abscessus + others
  • Oral + IV

321.3.3 High-Yield Specialist Points

321.3.3.1 Treatment Failure

  • Persistent positive cultures after 6 months
  • Re-evaluate:
    • Drug susceptibility
    • Adherence
    • Drug levels (e.g., azithromycin)
    • Surgery as adjunct
    • ALIS

321.3.3.2 M. abscessus + Lung Transplant

  • Many centers exclude active M. abscessus
  • Pre-transplant treatment + clearance preferred
  • Post-transplant recurrence common

321.3.3.3 NTM in HIV (Post-ART Era)

  • Less common with ART
  • CD4 < 50: still significant risk
  • Prophylaxis with azithromycin if CD4 < 50 + ART
  • Discontinue prophylaxis if CD4 > 100 × 3 months

321.3.3.4 Disseminated NTM

  • M. avium most common in HIV
  • M. genavense, M. haemophilum, others in HIV
  • Multi-organ
  • Bone marrow biopsy for diagnosis
  • Macrolide + ethambutol + rifabutin

321.3.3.5 Surgical Resection Indications

  • Localized cavitary disease
  • Drug-resistant
  • Hemoptysis
  • Persistent symptoms
  • Combined with antibiotics

321.3.3.6 Adverse Effects Monitoring

  • Azithromycin: QT prolongation, hearing loss, hepatotoxicity
  • Ethambutol: optic neuritis (vision baseline + monitoring)
  • Rifampin: hepatotoxicity, drug interactions
  • Amikacin: ototoxicity, nephrotoxicity
  • Clofazimine: skin discoloration, GI

321.3.3.7 Drug Susceptibility Testing

  • Standard for MAC: macrolide
  • M. abscessus: macrolide + amikacin + imipenem
  • More extensive for refractory cases
  • erm(41) gene testing for M. abscessus

321.3.3.8 NTM + Sarcoidosis

  • Granulomatous diseases overlap
  • Distinguish carefully
  • May coexist

321.3.3.9 M. chimaera Cardiac Surgery

  • 2014 outbreak from heater-cooler units
  • Disseminated infection (cardiac, ocular, bone marrow)
  • Long incubation (months-years post-surgery)
  • Treatment: prolonged multi-drug
  • Public health response important

321.3.3.10 Pediatric NTM

  • Cervical lymphadenitis (M. avium, M. scrofulaceum) most common
  • Treatment: surgical excision often curative
  • Disseminated in immunocompromised
  • HIV in pediatric: prophylaxis with azithromycin if low CD4

321.3.3.11 Future Directions

  • New antibiotics
  • Inhaled therapies expansion
  • Phage therapy (research)
  • Vaccine (early)
  • Better diagnostics (point-of-care)

321.3.4 Pearls

  • 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
  • MAC treatment: azithromycin + ethambutol + rifampin × 12 mo after conversion
  • CONVERT 2018: ALIS for refractory MAC
  • M. kansasii: TB-like, R + I + E × 9-12 mo
  • Disseminated MAC: HIV CD4 < 50; rifabutin + macrolide + ethambutol
  • Prophylaxis azithromycin if HIV + CD4 < 50