• See Also
  1. Tuberculosis
  2. Latent Tuberculosis Treatment
  3. Active Tuberculosis Treatment
  4. Possibly Resistant Tuberculosis Treatment
  5. Multiple Drug Resistant Tuberculosis Treatment
  6. Tuberculosis Screening in Children
  7. Tuberculosis Risk Factors (Tuberculosis Screening Indications)
  8. Tuberculosis Risk Factors for progression from Latent to Active Disease (Latent Tuberculosis Treatment Indications)
  9. Tuberculosis Related Chest XRay Changes
  10. Extrapulmonary Tuberculosis
  11. Tuberculin Skin Test (TST, Purified Protein Derivative, PPD)
  12. Mycobacterium Tuberculosis Antigen-Specific Interferon-Gamma Release Assay (IGRA)
  13. Tuberculosis Resources
  • Indications
  1. Resistance rate in patient's Community <4%
    1. Most communities have Tb resistance >4%
  2. HIV Screening negative
  3. Immunocompetent
  4. No prior Tuberculosis Treatment
  1. Background
    1. All but 1 of the medications are taken everyday with food for entire 119 day course
    2. Pyrazinamide is taken only for first 56 days only
    3. Shortens the course (better compliance)
    4. Reduces adverse effects compared to older regimens (reduced hepatotoxicity and ocular toxicity risk)
  2. Indications
    1. Age =12 years AND body weight =40 kg
    2. Pulmonary TB caused by organisms that are not known or suspected to be drug-resistant
  3. Contraindications
    1. Age <12 years or weight <40 kg
      1. Use the Ethambutol/Rifampin protocol for total of 4 months instead (see below)
    2. Pregnancy or Breastfeeding
      1. Requires 24 week course with a different regimen
    3. Extrapulmonary Tuberculosis (esp. CNS involvement)
  4. Phase 1: Intensive for first 8 weeks
    1. Rifapentine (RPT) 1200 mg orally daily
      1. Multiple Drug Interactions (HIV Medications, Opioids, contraceptives)
    2. Moxifloxacin (MOX) 400 mg orally daily
      1. Drug Interactions with iron, Magnesium and other cations
      2. Risk of QTc Prolongation
    3. Isoniazid (INH) 300 mg orally daily
      1. Take with Pyridoxine 25 to 50 mg orally daily (Peripheral Neuropathy prevention)
    4. Pyrazinamide (PZA, used for only first 8 weeks)
      1. Weight 40 to 55 kg: 1000 mg orally daily
      2. Weight 55 to 75 kg: 1500 mg orally daily
      3. Weight >75 kg: 2000 mg orally daily
  5. Phase 2: Continuation for additional 9 weeks
    1. Rifapentine (RPT) 1200 mg orally daily
    2. Moxifloxacin (MOX) 400 mg orally daily
    3. Isoniazid (INH) 300 mg orally daily
  6. References
    1. Carr (2022) MMWR Morb Mortal Wkly Rep 71(8):285-289 +PMID: 35202353 [PubMed]
  • Management
  • Four Drug Therapy with Ethambutol and Rifampin 4-6 Month Course (Older Regimen)
  1. Background
    1. Adults and teens are recommended to have the above 4 month course (with Moxifloxacin and Rifapentine)
    2. Additional regimens are available with less frequent dosing, but with higher risk of failure
    3. See CDC website for other regimens
  2. Initial/Intensive phase: 3-4 drug regimen for 2 months
    1. Medications (4 used together in initial phase)
      1. Isoniazid (INH)
        1. Adult: 300 mg orally daily
        2. Child: 10 to 15 mg/kg (up to 300 mg) orally daily
        3. Take with Pyridoxine 25 to 50 mg orally daily (Peripheral Neuropathy prevention)
      2. Rifampin (RIF)
        1. Adult: 10 mg/kg/day (up to 600 mg) oral or IV daily
        2. Child: 10 to 20 mg/kg/day (up to 600 mg) oral or IV daily
        3. Multiple Drug Interactions (HIV Medications, Opioids, contraceptives)
      3. Pyrazinamide (PZA)
        1. Weight <40 kg: 35 mg/kg (up to 1000 mg) orally daily
        2. Weight 40 to 55 kg: 1000 mg orally daily
        3. Weight 55 to 75 kg: 1500 mg orally daily
        4. Weight >75 kg: 2000 mg orally daily
      4. Ethambutol (EMB, unless not indicated by culture)
        1. Dose based on estimated Lean Body Mass and reduce dose in Renal Insufficiency
        2. Child: 15-25 mg/kg (max 1000 mg/day) orally daily
        3. Adult: 15-25 mg/kg (max 1600 mg/day) orally daily
          1. Weight 40 to 55 kg: 800 mg/day
          2. Weight 56 to 75 kg: 1200 mg/day
          3. Weight 79 to 90 kg: 1600 mg/day
    2. Dose timing
      1. Take all four medications once daily for 8 weeks (56 doses, preferred) OR
      2. Take five times weekly for 8 weeks (40 doses)
        1. Given under direct observation
  3. Continuation phase: Double therapy for 2-7 months
    1. Medications (2 used together in continuation phase)
      1. Isoniazid (INH)
      2. Rifampin (RIF)
    2. Dose timing (18 weeks unless otherwise noted below)
      1. Once daily for 9 weeks has replaced longer courses
      2. Once daily (125 doses, preferred) or
      3. Five times per week (90 doses, under direct observation, preferred) or
      4. Three times per week (54 doses under direct observation, alternative when direct observation schedule is difficult)
    3. Duration of treatment
      1. Double therapy for 18 weeks unless exceptions below
      2. Indications for 7 month continuation phase
        1. Cavitary pulmonary Tuberculosis
        2. Positive Sputum Culture after initial phase
  4. Adjunctive
    1. Vitamin B6 (Pyridoxine) 25-50 mg daily
      1. Indicated for Neuropathy risk due to INH (e.g. Diabetes Mellitus, Alcoholism)
      2. See Isoniazid for details
  • Labs
  • Monitoring
  1. Liver Function Tests
    1. Obtain baseline and every 3 months during therapy
  2. Serum Creatinine
    1. Obtain baseline and periodically ()
    2. Adjust doses of Ethambutol and Pyrazinamide accordingly
  • Resources
  1. CDC Tb Guidelines Treatment
    1. http://www.cdc.gov/tb/publications/guidelines/treatment.htm
  2. CDC Division of Tuberculosis Elimination
    1. http://www.cdc.gov/nchstp/tb/
  • References
  1. (2003) MMWR Morb Mortal Wkly Rep 52(RR-11):1 [PubMed]
  2. Nahid (2016) Clin Infect Dis 63(7): e147-95 [PubMed]