Active Tuberculosis Treatment

Aka: Active Tuberculosis Treatment, Active Tuberculosis, Active Tb Treatment, Active Tb, Active Tuberculosis Special Circumstances, Drug-Induced Hepatitis from Antituberculous Drugs

1. See Also
   1. Tuberculosis
   2. Tuberculosis Screening in Children
   3. Tuberculosis Risk Factors (Tuberculosis Screening Indications)
   4. Tuberculosis Risk Factors for progression from Latent to Active Disease (Latent Tuberculosis Treatment Indications)
   5. Tuberculosis Related Chest XRay Changes
   6. Extrapulmonary Tuberculosis
   7. Tuberculin Skin Test (TST, Purified Protein Derivative, PPD)
   8. Mycobacterium Tuberculosis Antigen-Specific Interferon-Gamma Release Assay (IGRA)
   9. Latent Tuberculosis Treatment
   10. Susceptible Tuberculosis Treatment
   11. Possibly Resistant Tuberculosis Treatment
   12. Multiple Drug Resistant Tuberculosis Treatment
   13. Tuberculosis Resources
2. Diagnosis
   1. See Tuberculosis
   2. Requires idenitifying acid fast Bacteria
   3. Tuberculosis Screening (TST, IGRA) is insufficient to diagnose Active Tb
3. Precautions
   1. Tuberculosis requires long-term treatment
      1. Requires at least 6 months of medications (extended as long as 24 months in some cases)
   2. Regimens for Tuberculosis treatment must be multi-drug
      1. Four drugs should be used initially until culture (returned by 6-8)
      2. Never add a single drug to a failing regimen
      3. Avoid the Susceptible Tb Treatment protocol in suspected resistant Tuberculosis
         1. See Possibly Resistant Tb Treatment
         2. See Multiple Drug Resistant Tb Treatment
   3. Patients must be monitored at least monthly
   4. Patient noncompliance is a major problem
      1. Consider intermittent therapy
      2. Consider Directly observed therapy
   5. Patients must be isolated (quarantined) until non-infectious
      1. Patient should stay in their home and wear a mask around others (or negative airflow room in facility)
      2. Non-infectious status is confirmed with three induced Sputum samples negative for acid-fast Bacteria
      3. Patients become non-infectious at 2-4 weeks after initiating antibiotics
4. Drug Interactions
   1. Review Drug Interactions before use (esp. Rifampin)
5. Adverse Effects: Tuberculosis Medications
   1. Gastrointestinal upset
      1. Consider taking medication with food
      2. Consider Antacid use
   2. Hepatotoxin (AST 3-5x normal)
      1. See Also Hepatotoxin
      2. Consider alternatives below if advanced liver disease
      3. Drugs most likely to cause Drug-Induced Hepatitis
         1. Isoniazid
         2. Rifampin
         3. Pyrazinamide
      4. Alternative drugs if Drug-Induced Hepatitis occurs
         1. Capreomycin
         2. Fluoroquinolone
         3. Ethambutol
         4. Streptomycin
         5. Amikacin
         6. Kanamycin
   3. Peripheral Neuropathy
      1. Isoniazid (INH)
   4. Optic Neuritis
      1. Ethambutol (EMB)
   5. Gout
      1. Pyrazinamide (PZA)
   6. Ototoxicity
      1. Streptomycin (and other Aminoglycosides)
   7. Renal Toxin
      1. Streptomycin (and other Aminoglycosides)
   8. Discolored body fluids
      1. Rifampin causes red-orange Urine Color, stool color, Saliva, sweat and tears
6. Labs
   1. Obtain 3 initial Acid-fast bacilli smears and cultures (or DNA testing)
      1. Repeat testing monthly until 2 consecutive tests are negative
   2. Acid-fast bacilli smears, DNA and cultures are critical to management
      1. Determine the drug regimen used
      2. Determine the duration of the continuation phase of treatment
7. Management: Protocols
   1. Susceptible Tb Treatment
   2. Possibly Resistant Tb Treatment
   3. Multiple Drug Resistant Tb Treatment
8. Management: Standard Adult
   1. See Susceptible Tb Treatment
   2. Precautions
      1. This protocol assumes susceptible Tuberculosis
         1. See Susceptible Tb Treatment for complete description and indications
      2. Avoid this protocol in suspected resistant Tuberculosis
         1. See Possibly Resistant Tb Treatment
         2. See Multiple Drug Resistant Tb Treatment
   3. First 2 months: Four drug regimen
      1. Isoniazid
      2. Rifampin
      3. Pyrazinamide
      4. Ethambutol
   4. Next 4 months (extend to 7-10 months if Immunocompromised)
      1. Isoniazid
      2. Rifampin
   5. Monitoring
      1. Monitor Serum Creatinine (adjust doses of Ethambutol and Pyrazinamide accordingly)
   6. 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
9. Management: Special Circumstances
   1. Human Immunodeficiency Virus Infection
      1. Avoid once weekly continuation phase protocols
   2. Pediatric patients
      1. Start empiric treatment immediately if suspected
         1. High risk of Disseminated tuberculosis
      2. Initial Protocol
         1. Three drug regimen indicated in most cases (contrast with adults where 4 drug regimen used)
            1. Regimen: Isoniazid, Pyrazinamide, Rifampin
            2. Ethambutol avoided due to decreased Vision risk
         2. Four drug regimen (inc. Ethambutol) indications
            1. Upper lobe infitrate
            2. Cavitation
            3. Productive cough
   3. Pregnant Women
      1. Initial Regimen: Isoniazid, Rifampin, Ethambutol
      2. Give Pyridoxine 25 mg daily (prevents Neuropathy)
      3. Do not use Streptomycin in pregnancy
      4. Pyrazinamide appears safe in pregnancy
         1. Less studied, and avoided in some regimens
         2. Give 7 month continuation phase if no Pyrazinamide
   4. Lactation
      1. May continue to Breast feed on antituberculous drugs
      2. Give Pyridoxine 25 mg daily (prevents Neuropathy)
10. Management: Non-compliance
    1. General
       1. Compliance management is imperative
       2. Non-compliance causes treatment failures, resistance
    2. Dosing should be observed unless compliance assured
    3. Consider fixed dose combinations
       1. Rifater
          1. Contents
             1. Rifampin 120 mg
             2. Isoniazid 50 mg
             3. Pyrazinamide 300mg
          2. Treat for first 2 months of daily therapy
             1. Weight <44 kg: 4 tabs qd
             2. Weight 45-54 kg: 5 tabs qd
             3. Weight >55 kg: 6 tabs qd
       2. Rifamate
          1. Rifampin 300 mg
          2. Isoniazid 150 mg
11. Resources
    1. CDC Tb Guidelines Treatment
       1. http://www.cdc.gov/tb/publications/guidelines/treatment.htm
12. References
    1. (2016) Presc Lett 23(10)
    2. Swadron (2019) Pulmonology 2, CCME Emergency Medicine Board Review, accessed 6/16/2019
    3. Frieden (2003) Lancet 362:887-99 [PubMed]
    4. Nahid (2016) Clin Infect Dis 63(7): e147-95 [PubMed]
    5. Potter (2005) Am Fam Physician 72:2225-35 [PubMed]