320.1 🎓 醫孞生版

320.1.0.1 📌 䞀頁重點

320.1.0.1.1 Epidemiology
  • ~ 10 million new TB cases / yr globally
  • 1.5 million deaths / yr
  • ~ 1/4 world’s population latently infected
  • Taiwan: incidence ~ 35-40 / 100,000; intermediate-high
  • HIV co-infection major risk
  • MDR-TB 3-5% globally; XDR rare but serious
320.1.0.1.2 Microbiology
320.1.0.1.2.1 Mycobacterium tuberculosis
  • Acid-fast bacillus (AFB)
  • Slow-growing (doubling 18-24 hours)
  • Aerobic; intracellular survival in macrophages
  • Mycolic acid cell wall (resistant to many antibiotics)
  • Transmission: respiratory droplets (cough, sneeze, singing, etc.)
320.1.0.1.2.2 Other Mycobacteria
  • NTM (Ch320)
  • M. leprae (leprosy)
320.1.0.1.3 Pathogenesis
320.1.0.1.3.1 Primary Infection
  • Inhaled droplets → alveolar macrophages
  • Most contained → latent
  • ~ 5% progress to primary disease in 1-2 years
  • ~ 5% additional lifetime reactivation
  • HIV: 5-15% / year reactivation
320.1.0.1.3.2 Latent TB (LTBI)
  • Asymptomatic
  • Immune-controlled
  • Positive IGRA / TST
  • Normal CXR
  • Risk of reactivation (immunosuppression, age, comorbidities)
320.1.0.1.3.3 Active TB
  • Symptomatic
  • Bacterial multiplication
  • Caseating granulomas
  • Cavity formation
  • Transmissible
320.1.0.1.4 Risk Factors
320.1.0.1.4.1 For TB Infection
  • Close contact with active TB
  • Healthcare workers
  • Endemic country immigrants/travelers
  • Homeless, incarcerated
  • Crowded living conditions
  • IDU
320.1.0.1.4.2 For TB Progression (LTBI → Active)
  • HIV (100x risk)
  • Recent infection (within 2 years)
  • Young children (< 5)
  • Elderly
  • Diabetes mellitus (3-4x)
  • Chronic kidney disease + dialysis
  • Malnutrition (low BMI)
  • Smoking
  • Silicosis (5x)
  • Solid organ transplant
  • TNF-α inhibitors (infliximab, adalimumab — 5-10x)
  • JAK inhibitors (tofacitinib)
  • Corticosteroids (≥ 15 mg prednisone × 4 wk)
  • Cancer chemotherapy
320.1.0.1.5 Clinical Features
320.1.0.1.5.1 Pulmonary TB

Symptoms (often insidious, weeks-months): - Chronic cough (> 2-3 weeks) - Fever (often low-grade, evening) - Night sweats - Weight loss - Hemoptysis - Pleuritic chest pain - Fatigue, anorexia

Examination: - Crackles, decreased breath sounds in affected area - Often normal - Lymphadenopathy (cervical, mediastinal) - Signs of pleural effusion

320.1.0.1.5.2 Extrapulmonary TB (40% of cases, more in HIV)
  • Lymphadenitis (cervical = scrofula)
  • Pleural (TB pleurisy; ADA > 40)
  • Pericardial
  • Miliary (disseminated, multi-organ)
  • Renal / genitourinary
  • CNS (meningitis, tuberculoma)
  • Bone / joint (Pott’s disease)
  • Abdominal (peritoneal, intestinal)
  • Cutaneous
320.1.0.1.6 Diagnosis
320.1.0.1.6.1 Latent TB Infection (LTBI)

Tuberculin Skin Test (TST / Mantoux): - 5 TU PPD intradermal - Read 48-72 hours - Measured induration (mm) - Interpretation: - ≥ 5 mm: HIV, recent contact, CXR abnormal, immunosuppressed, organ transplant - ≥ 10 mm: immigrants from endemic area, IDU, healthcare workers, congregate settings, children, comorbidities (DM, CKD) - ≥ 15 mm: low-risk individuals - BCG vaccination can cause false positives

Interferon-Gamma Release Assay (IGRA): - QuantiFERON Gold Plus (QFT) or T-SPOT.TB - ELISA-based; measures IFN-γ release after TB antigen exposure - Not affected by BCG (preferred in Taiwan + vaccinated populations) - Single blood draw - Specific for M. tuberculosis complex - Preferred over TST in BCG-vaccinated

LTBI Diagnosis: - Positive IGRA or TST - No symptoms - Normal CXR - Confirms LTBI

320.1.0.1.6.2 Active TB

Clinical Features + CXR: - Symptoms compatible - Upper lobe involvement (postprimary): infiltrates, cavities, fibronodular - Primary: lower lobe + hilar LAD (Ghon complex)

Sputum Testing: - AFB Smear (Ziehl-Neelsen or auramine): - 3 samples (early morning preferred) - Sensitivity 50-80% - “Smear-positive” = highly infectious - Mycobacterial Culture: - Gold standard - 2-6 weeks for results - Allows drug susceptibility testing (DST) - NAAT (Nucleic Acid Amplification Test): - Xpert MTB/RIF (or Ultra): rapid (~ 2 hours) - Detects M. tuberculosis + rifampin resistance - Sensitivity 85-95% in smear-positive, 70-75% in smear-negative - WHO + IDSA Class I for initial diagnosis

Bronchoscopy if sputum unobtainable

Tissue Biopsy for extrapulmonary

Imaging: - CXR: upper lobe cavities, nodular, miliary, hilar LAD - CT: better for cavities, miliary, extrapulmonary - PET: monitoring (research mostly)

320.1.0.1.6.3 Drug Susceptibility Testing (DST)
  • Phenotypic: 2-6 weeks for cultures
  • Genotypic (rapid):
    • Xpert MTB/RIF: rifampin resistance
    • Xpert MTB/XDR: also INH, fluoroquinolone, aminoglycoside, ethionamide resistance
    • Line probe assay (Genotype MTBDR)
320.1.0.1.7 Treatment
320.1.0.1.7.1 Latent TB Infection (LTBI)

Indications: - High-risk for progression - HIV - Recent contact - Pre-TNF-α inhibitor - Organ transplant - Selected with risk factors

Regimens (2020 ATS/CDC/IDSA Update):

  1. 3HP: Rifapentine + Isoniazid weekly × 12 weeks (preferred, often DOT)
  2. 4R: Rifampin daily × 4 months (preferred for INH intolerance)
  3. 3HR: Isoniazid + Rifampin daily × 3 months
  4. 9H: Isoniazid daily × 9 months (older standard)

Considerations: - Drug interactions (rifamycins induce CYP enzymes — affect contraceptives, anticoagulants, HIV ART) - Pyridoxine (B6) with INH (prevent peripheral neuropathy) - Hepatotoxicity monitoring (LFTs)

320.1.0.1.7.2 Active TB

Drug-Susceptible TB (DS-TB):

Standard 6-Month Regimen: - Intensive phase (2 months): RIPE - Rifampin - Isoniazid (+ pyridoxine) - Pyrazinamide - Ethambutol - Continuation phase (4 months): RI - Rifampin + Isoniazid

Total: 6 months

Drug Doses (Daily): - Rifampin 10 mg/kg (max 600 mg) - Isoniazid 5 mg/kg (max 300 mg) - Pyrazinamide 25 mg/kg (max 2000 mg) - Ethambutol 15-25 mg/kg (max 1600 mg) - Pyridoxine 25-50 mg/day with INH

Side Effects: - Rifampin: orange body fluids, hepatotoxicity, drug interactions (CYP induction), thrombocytopenia, flu-like syndrome (intermittent) - Isoniazid: hepatotoxicity, peripheral neuropathy (pyridoxine prevention), drug-induced lupus - Pyrazinamide: hepatotoxicity, hyperuricemia (gout), arthralgia - Ethambutol: optic neuritis (color vision + visual acuity baseline) - Streptomycin (rarely used): ototoxicity, nephrotoxicity

Monitoring: - LFTs monthly (more if abnormal or symptoms) - Vision (ethambutol) - Adherence (sputum cultures monthly)

Special Situations: - Cavitary disease + culture-positive at 2 months → extend continuation to 7 months (total 9 months) - TB meningitis: 12 months minimum + corticosteroids - TB pericarditis: 6 months + corticosteroids - Pott’s disease: 12 months - Bone / joint: 6-9 months - HIV: standard but watch for IRIS, drug interactions

320.1.0.1.7.3 MDR-TB (Multidrug-Resistant)

Definition: Resistant to INH + RIF (at minimum)

Pre-2022 Regimens: - 4-7 drugs × 18-24 months - High side effect profile - Mixed results

Post-2022 BREAKTHROUGH: BPaL Regimen - Bedaquiline + Pretomanid + Linezolid - Nix-TB (2020) + ZeNix (2022) trials - 6 months total - Effective for MDR + extensively drug-resistant TB - WHO 2022 endorsement - Game-changer

BPaLM (Bedaquiline + Pretomanid + Linezolid + Moxifloxacin): - 6 months - For MDR-TB - WHO 2022 endorsement - TB-PRACTECAL trial 2022

320.1.0.1.7.4 XDR-TB (Extensively Drug-Resistant)
  • MDR + resistance to fluoroquinolones + at least one injectable (amikacin, kanamycin, capreomycin)
  • Pre-XDR: MDR + fluoroquinolone OR injectable
  • BPaL/BPaLM also covers XDR
320.1.0.1.8 Special Populations
320.1.0.1.8.1 HIV Co-Infection
  • ART + TB treatment together
  • Drug interactions (rifampin + protease inhibitors)
  • Rifabutin alternative (less interaction)
  • IRIS (Immune Reconstitution Inflammatory Syndrome): worsening symptoms 4-8 weeks after ART start; manage with continued ART + steroids
  • Earlier ART preferred (within 2 weeks if low CD4)
320.1.0.1.8.2 Pregnancy
  • Treat active TB (risk of untreated > drugs)
  • INH + RIF + EMB usually OK
  • Avoid pyrazinamide (debated, theoretical teratogenicity; not FDA-approved in pregnancy)
  • Add pyridoxine
  • Streptomycin contraindicated (fetal ototoxicity)
  • Postpartum BCG? Avoid in HIV
320.1.0.1.8.3 Pediatric
  • Modified doses
  • Same general principles
  • INH + RIF base
  • BCG vaccination in many countries (early infant)
320.1.0.1.8.4 Hepatotoxicity
  • LFT > 3x ULN with symptoms OR > 5x ULN asymptomatic → hold hepatotoxic drugs
  • Use non-hepatotoxic regimen: EMB + streptomycin + fluoroquinolone
  • Re-introduce single agents to identify
  • Liver consult
320.1.0.1.9 Public Health
320.1.0.1.9.1 Reporting
  • TB is reportable disease (mandatory)
  • Contact tracing
  • DOT (directly observed therapy) standard
  • Public health departments
320.1.0.1.9.2 Infection Control
  • Airborne precautions (N95 mask, negative pressure room) until non-infectious
  • Smear conversion + 2 weeks effective therapy + clinical improvement = generally non-infectious
  • Isolation: 3 consecutive smear-negative samples (≥ 8 hr apart)
320.1.0.1.9.3 BCG Vaccine
  • For neonates in endemic countries
  • Protection against severe pediatric forms (miliary, meningeal)
  • Less protection against pulmonary in adults
  • Causes false-positive TST
  • Generally one-time vaccine

320.1.0.2 🩺 床邊速查

  • Active TB diagnosis: AFB smear + culture + Xpert MTB/RIF NAAT (Class I)
  • LTBI: IGRA preferred (BCG no interference); TST acceptable
  • Standard treatment: RIPE × 2 months → RI × 4 months (total 6)
  • Drug side effects: R (orange urine, CYP), I (neuropathy, give B6), P (hepatic, gout), E (optic neuritis)
  • MDR-TB: BPaL/BPaLM × 6 months (Nix-TB, ZeNix, TB-PRACTECAL)
  • LTBI: 3HP (rifapentine + INH weekly × 12 weeks) preferred
  • HIV + TB: ART within 2 weeks; rifabutin if drug interactions; watch IRIS