Tuberculosis 07/18/2017

  • Definitions
    • Primary Tuberculosis
      • 1-5% of cases
      • Infection directly after inoculation by airborne particles
      • Symptoms
        • Fever (70%)
        • Pleuritic chest pain (25%)
      • 90% of immunocompetent patient enter latent state
        • 10% develop TB pneumonia or progress to distant sites
          • Usually those with poor immune responses (HIV, CKD, DM2, immunosuppressants)
    • Latent TB (LTBI)
      • Non-contageous, quiescent state
      • Only manifestation is positive PPD or Quantiferon (IGRA – interferon gamma release assay)
    • Reactivation TB
      • 90% of adult cases in non-HIV patients
      • Classic symptoms
        • Cough, fatigue, fever, night sweats, weight loss
          • Sometimes hemoptysis –> usually in the setting of cavitary disease
  • Risk Factors
    • For exposure
      • Foreign born
      • Homeless
      • Incarceration
      • Health care workers
    • For reactivation
      • Immunocompromised
        • HIV, malignancy, steroids, DM2
      • Prior untreated or inadequately treated disease
      • Lifetime risk for reactivation
        • Immunocompetent -> 10% lifetime risk
        • Immunocompromised -> 10% per year
  • Physical finding –> non-specific and usually absent in mild-moderate disease
  • Labs
    • Sputum samples
      • AFB smear/culture
        • Obtained by coughing vs induced (inhalation of hypertonic saline from nebulizer)
        • 3 specimens at least 8 hours apart
        • Most rapid and inexpensive test
          • 45-80% sensitive
        • AFB positive smear can represent non-tuberculosis mycobacteria (NTM) as well
          • Must confirm with culture and nucleic acid amplification
      • Nucleic acid amplification (NAA) tests
        • Xpert MTB/RIF Test
          • Detects MTB DNA and rifampin resistance mutations
            • But cannot provide specific sequence information
          • Smear positive sample –> 95% sensitive, 98% specific
          • Smear negative sample –> 80% sensitive, 95% specific
          • Negative Xpert cannot exclude active TB!
          • Watch out for false positives from recent previously treated infection
      • Sequencing assays
        • Sequencing assays provide specific sequence mutations and predicts drug resistance with greater accuracy
          • Not approved by FDA; Remains investigational
    • Tuberculin Skin Test (TST) and quantiferon
      • Only used to diagnose latent TB infection, not active TB!
      • Positive result supports Dx; negative result cannot be used to rule out
  • Imaging
    • CXR
      • Primary TB
        • Hilar and peritracheal lymphadenopathy (65%)
        • Small homogeneous lobar vs perihilar infiltrates (30%)
        • Pleural effusion (30%)
      • Reactivation TB
        • Normal hosts
          • apical-posterior infiltrates (85%)
            • MTB prefers higher O2 tensions in the apical lung areas
            • poor lymphatic flow in apices results in poor organism clearance
          • cavitation
        • Immunocompromised (AIDS) Pts –> Atypical findings
          • Diffuse disease (military)
          • Mid/lower lung zones
          • Hilar and mediastinal LAD
        • CT
          • More sensitive than plain CXR for early or subtle parenchymal and nodal disease
  • Management
    • General approach
      • 6 months of treatment in 2 phases
        • Intensive phase –> 2 months
          • First line drugs –> “RIPE”
            • Rifampin, INH, pyrazinamide, ethambutol
        • Continuation phase –> 4 months
          • Rifampin
          • INH
    • Watch out for hepatotoxicity!
      • Rifampin, INH, and pyrazinamide are all associated with hepatotoxicity
    • All pts in INH should get vit B6
    • Avoid fluoroquinolones in suspected TB cases!
      • Avoid resistance from TB monotherapy

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