Active Tuberculosis Treatment

See Also

Diagnosis

See Tuberculosis
Requires idenitifying Acid Fast Bacteria
Tuberculosis Screening (TST, IGRA) is insufficient to diagnose Active Tb

Precautions

Tuberculosis requires long-term treatment
1. Requires at least 4 months of medications (extended as long as 24 months in some cases)
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
Patients must be monitored at least monthly
Patient noncompliance is a major problem
1. Consider intermittent therapy
2. Consider Directly observed therapy
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

Drug Interactions

Review Drug Interactions before use (esp. Rifampin)

Adverse Effects
Tuberculosis Medications

Gastrointestinal upset
1. Consider taking medication with food
2. Consider Antacid use
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 (less with Rifapentine)
  3. Pyrazinamide
4. Alternative drugs if Drug-Induced Hepatitis occurs
  1. Capreomycin
  2. Fluoroquinolone
  3. Ethambutol
  4. Streptomycin
  5. Amikacin
  6. Kanamycin
Peripheral Neuropathy
1. Isoniazid (INH)
Optic Neuritis
1. Ethambutol (EMB)
Gout
1. Pyrazinamide (PZA)
Ototoxicity
1. Streptomycin (and other Aminoglycosides)
Renal Toxin
1. Streptomycin (and other Aminoglycosides)
Discolored body fluids
1. Rifampin causes red-orange Urine Color, stool color, Saliva, sweat and tears

Labs

Obtain 3 initial Acid-fast bacilli smears and cultures (or DNA testing)
1. Repeat testing monthly until 2 consecutive tests are negative
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

Management
Protocols

Management
Standard Adult

See Susceptible Tb Treatment
Background
1. Four Drug Therapy with Moxifloxacin and Rifapentine 4 Month Course (2022 Regimen)
2. This protocol assumes susceptible Tuberculosis
  1. See Susceptible Tb Treatment for complete description and indications
3. Avoid this protocol in suspected resistant Tuberculosis
  1. See Possibly Resistant Tb Treatment
  2. See Multiple Drug Resistant Tb Treatment
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
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)
Phase 1: Intensive for first 8 weeks
1. Rifapentine (RPT) 1200 mg orally daily
2. Moxifloxacin (MOX) 400 mg orally daily
3. Isoniazid (INH) 300 mg orally daily
4. Pyrazinamide (PZA) 1000, 1500 or 2000 mg (based on weight <55 kg, 55-75 kg, or >75 kg)
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
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
Monitoring
1. Liver Function Tests at baseline and 3 months
2. Renal Function baseline (may affect Pyrazinamide dosing)
References
1. Carr (2022) MMWR Morb Mortal Wkly Rep 71(8):285-289 +PMID: 35202353 [PubMed]

Management
Special Circumstances

Human Immunodeficiency Virus Infection
1. Avoid once weekly continuation phase protocols
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
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
Lactation
1. May continue to Breast feed on antituberculous drugs
2. Give Pyridoxine 25 mg daily (prevents Neuropathy)

Management
Non-compliance

General
1. Compliance management is imperative
2. Non-compliance causes treatment failures, resistance
Dosing should be observed unless compliance assured
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

Resources

CDC Tb Guidelines Treatment
1. http://www.cdc.gov/tb/publications/guidelines/treatment.htm

References

(2016) Presc Lett 23(10)
Swadron (2019) Pulmonology 2, CCME Emergency Medicine Board Review, accessed 6/16/2019
Frieden (2003) Lancet 362:887-99 [PubMed]
Nahid (2016) Clin Infect Dis 63(7): e147-95 [PubMed]
Potter (2005) Am Fam Physician 72:2225-35 [PubMed]

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