11- TB Tx

• Treatment

  1. Intensive phase

  2. Continuation phase
• Intensive phase

  • Isoniazid, Rifampin, Pyrazinamide, Ethambutol administered for 2 months
  • Re-assess the patient when this phase is completed
• Continuation phase

  • Consists of isoniazid and rifampin administered for 4 months
  • May be extended up to 7 months
• Reasons for extending continuation phase

  • Patients with both cavitary pulmonary TB on initial CXR and positive sputum culture after the 2-month intensive-phase treatment
  • Intensive phase did not include 2 months of pyrazinamide
  • Some patients with HIV co-infection
• Continuation phase for HIV-uninfected patients

  • Shortened to 2 months for patients with negative sputum cultures and symptomatic and/or radiographic improvement in the absence of an alternative diagnosis
• Daily therapy is preferred over intermittent therapy during both phases (esp. intensive phase)
• Dexamethasone is added as adjunct in treatment initiation in CNS and pericardial disease (decreases risk of constrictive pericarditis & neurological complications)
• Baseline liver function (bilirubin, ALP, transaminases) must be established before treatment due to risk of hepatotoxicity
• Asymptomatic aminotransferase elevations resolve spontaneously over days to weeks in most patients
• Drug-induced hepatitis

  1. Stop all hepatotoxic drugs if bilirubin ≥3 mg/dL or transaminases >3-5 times the upper limit of normal

  2. Once LFTs return to baseline (or fall to less than twice normal), hepatotoxic drugs can be restarted one at a time with careful monitoring between resumption of each agent
• Treatment failure

  Positive cultures after 4 months of therapy
• Relapse


  Recurrent tuberculosis at any time after completion of treatment with apparent cure
• Isoniazid

  Inhibits cell wall synthesis
• Isoniazid side effects

  • Allergic reactions, rash, peripheral neuropathy: polyneuropathy & paresthesia (give pyridoxine Vit B6)
• Rifampicin

  Inhibits DNA-dependent RNA synthesis by inhibiting RNA polymerase
• Rifampicin side effects

  • Stain body secretions pink (urine, tears, sweat), thrombocytopenia
  • Induces liver enzymes (drugs cleared by liver enzymes won't be as effective. ex: OCPs, antidepressants, anticoagulants, antiepileptics)
• Pyrazinamide

  Prodrug; converted to pyrazinaid acid, accelerate effect of isoniazid & rifampicin. May inhibit fatty acid synthetase 1 of mycobacterium tuberculosis
• Pyrazinamide side effects

  • Hyperuricemia, gout, rash, arthralgia
  • Contraindicated in pregnancy
• Ethambutol

  Inhibits cell wall synthesis
• Ethambutol side effects

  • Optic neuritis, visual acuity, color blindness
  • Must decrease the dose in renal failure