320.3 🏥 內科專科考前版

320.3.1 Mechanistic Deep Dive

320.3.1.1 TB Granuloma

  • Macrophages, T cells (CD4 Th1 dominant)
  • Multinucleated giant cells (Langhans)
  • Caseating necrosis
  • TNF-α critical
  • IFN-γ critical

320.3.1.2 TB Drug Mechanisms

  • Isoniazid: inhibits mycolic acid synthesis (InhA + KatG)
  • Rifampin: RNA polymerase (RpoB)
  • Pyrazinamide: pyrazinamidase + low pH active in macrophages
  • Ethambutol: arabinogalactan (cell wall)
  • Streptomycin: 30S ribosome
  • Bedaquiline: ATP synthase
  • Pretomanid: nitroimidazo-oxazine (DNA + RNA synthesis)
  • Linezolid: 50S ribosome (also for MRSA)

320.3.1.3 Drug Resistance Mechanisms

  • INH: KatG mutation (50%); InhA promoter (~ 30%); other
  • RIF: RpoB mutation
  • Fluoroquinolone: GyrA mutation
  • PZA: pncA mutation
  • Genotypic testing for rapid detection

320.3.2 Recent Trials & Updates

320.3.2.1 Nix-TB (2020) — BPaL for MDR/XDR-TB

  • N = 109 MDR/XDR-TB + treatment-failure
  • BPaL × 6 months
  • 89% success
  • Revolution in MDR-TB treatment

320.3.2.2 ZeNix (2022)

  • Optimized linezolid dose (less toxicity)
  • Same efficacy
  • Practice-changing

320.3.2.3 TB-PRACTECAL (2022)

  • BPaLM × 6 months vs longer standard for MDR-TB
  • Superior efficacy + safety
  • WHO 2022 endorsement

320.3.2.4 3HP for LTBI

  • Comparable efficacy to 9H
  • Shorter, better adherence
  • DOT typically
  • Preferred over 9H now

320.3.2.5 iAdhere (2024)

  • Adherence monitoring with apps

320.3.2.6 TB Vaccine Development

  • M72/AS01E (Gates Foundation): phase 3
  • VPM1002, MTBVAC: phase 2-3
  • BCG re-vaccination studies
  • Hope for adult vaccine

320.3.2.7 COVID-19 + TB

  • Co-infection ↑ mortality
  • TB diagnosis delayed during pandemic
  • Resurgence concerns

320.3.3 High-Yield Specialist Points

320.3.3.1 Diagnosis Algorithm

  1. Symptoms compatible + risk factors
  2. CXR or CT
  3. Sputum AFB smear + culture + NAAT (Xpert MTB/RIF)
  4. Drug susceptibility testing (DST)
  5. HIV testing
  6. Treatment initiation
  7. Public health reporting

320.3.3.2 Sputum Conversion Monitoring

  • Monthly smear + culture
  • Conversion within 2 months expected
  • Failure → drug resistance, adherence, malabsorption
  • Extended treatment if persistent

320.3.3.3 TB + Diabetes

  • 3-4x higher TB risk
  • Both diseases reinforce each other
  • Poorer outcomes
  • Bidirectional screening
  • Aggressive DM control during TB

320.3.3.4 TB + TNF-α Inhibitors

  • 5-10x reactivation risk
  • Screen IGRA/TST before starting
  • Treat LTBI if positive
  • Some guidelines: continue biologic during LTBI treatment

320.3.3.5 TB Pericarditis

  • Effusive → effusive-constrictive → constrictive
  • ADA elevated in pericardial fluid
  • IMPI trial 2014: adjunctive prednisolone reduced hospitalization + constrictive pericarditis
  • Standard 6-month regimen

320.3.3.6 TB in End-Stage Renal Disease

  • Higher risk
  • Drug adjustments: rifampin OK, INH OK, EMB adjust (mostly renal excreted), PZA adjust
  • Watch ototoxicity (streptomycin)

320.3.3.7 Rifabutin vs Rifampin

  • Less CYP induction
  • Useful in HIV + protease inhibitors
  • Same TB efficacy

320.3.3.8 Drug Interactions

  • Rifampin induces CYP3A4 → reduces:
    • Contraceptives, warfarin, HIV protease inhibitors
    • Many other drugs
  • Switch to rifabutin or use alternative

320.3.3.9 Hepatotoxicity Management

  • Monitor LFTs monthly
  • Hold if ALT > 3x ULN + symptoms OR > 5x ULN asymptomatic
  • Re-introduce single drugs to identify culprit
  • Substitute non-hepatotoxic drugs (ethambutol + streptomycin + fluoroquinolone)
  • Liver consult

320.3.3.10 Pyridoxine (B6) with INH

  • 25-50 mg daily
  • Prevents peripheral neuropathy
  • Especially in: pregnancy, alcoholism, malnourished, DM, HIV, renal disease, breastfeeding

320.3.3.11 IRIS Management

  • Continue ART + TB treatment
  • Steroids for severe (Meintjes 2010)
  • NSAIDs for mild
  • Don’t stop therapies

320.3.3.12 Surgery in TB

  • For drug-resistant (MDR/XDR) refractory disease
  • Selected
  • Combined with multidrug therapy

320.3.3.13 TB-Lung Cancer Association

  • TB scar carcinoma (rare association)
  • Surveillance in TB survivors

320.3.4 Pearls

  • AFB smear + culture + Xpert MTB/RIF for active TB diagnosis
  • IGRA preferred for LTBI in BCG-vaccinated (Taiwan)
  • RIPE × 2 mo → RI × 4 mo standard
  • MDR-TB: BPaL/BPaLM × 6 months (Nix-TB, ZeNix, TB-PRACTECAL)
  • 3HP (rifapentine + INH weekly × 12 wk) preferred for LTBI
  • HIV + TB: ART within 2 weeks if low CD4; watch IRIS
  • TB meningitis: 12 mo + steroids
  • Reportable disease + airborne isolation + DOT
  • Ethambutol: optic neuritis (check vision)
  • Pyridoxine with INH