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Latent Tuberculosis Treatment
Aka: Latent Tuberculosis Treatment, Latent Tuberculosis, Latent Tb, Tuberculosis Prophylaxis, Tb Prophylaxis, LTBI
- See Also
- Tuberculosis
- Tuberculosis Screening in Children
- Tuberculosis Risk Factors (Tuberculosis Screening Indications)
- Tuberculosis Risk Factors for progression from Latent to Active Disease (Latent Tuberculosis Treatment Indications)
- Tuberculosis Related Chest XRay Changes
- Extrapulmonary Tuberculosis
- Tuberculin Skin Test (TST, Purified Protein Derivative, PPD)
- Mycobacterium Tuberculosis Antigen-Specific Interferon-Gamma Release Assay (IGRA)
- Active Tuberculosis Treatment
- Susceptible Tuberculosis Treatment
- Possibly Resistant Tuberculosis Treatment
- Multiple Drug Resistant Tuberculosis Treatment
- Tuberculosis Resources
- Epidemiology
- Concurrent HIV Infection confers a 10% conversion to Active Tuberculosis per year (highest rate)
- Overall rate of progression from Latent Tuberculosis to Active Tuberculosis: 5-15%
- Latent Tuberculosis progression is responsible for >80% of Active Tuberculosis cases in the United States
- Half of latent to Active Tuberculosis progressions occur within the first 2 years following infection
- Progression within 2 years in otherwise healthy patient (e.g. non-HIV): 5%
- Progression after 2 years in otherwise healthy patient (e.g. non-HIV): 5%
- Precautions
- Latent Tuberculosis is a lab diagnosis based on positive Screening Tests (IGRA, PPD)
- Latent Tuberculosis patients are asymptomatic
- Active Tuberculosis patients are symptomatic (cough, Hemoptysis, Night Sweats, weight loss)
- Active Tuberculosis patients are treated with multi-drug regimens to prevent resistance
- Do not treat Latent Tuberculosis patients with single agent until Active Tb is excluded by history
- Latent Tb management requires provider vigilence
- Educate and monitor compliance (important to complete course)
- Be alert for hepatotoxicity (Isoniazid, rifamycins) and limit Alcohol and other Hepatotoxins
- Observe for Thrombocytopenia with rifamycins
- See specific agents for additional recommendations (e.g. Vitamin B6 and Isoniazid, Rifamycin Drug Interactions)
- Indications: Strongest Indications for Latent Tuberculosis Treatment
- See Tuberculosis Screening (Tuberculin Skin Test or IGRA)
- See Tuberculosis Risk Factors for progression from Latent to Active Disease
- Risk of serious disease or Extrapulmonary Tuberculosis (e.g. Miliary Tuberculosis, Tuberculous Meningitis)
- Contraindications: Latent Tuberculosis Treatment
- Age over 35 years (risk of hepatitis) is no longer an absolute contraindication
- Prophylaxis indications regardless of age
- Recent PPD conversion
- Chest XRay shows healed Tuberculosis (see Tuberculosis Related Chest XRay Changes)
- Immunocompromised patient (e.g. HIV)
- Protocols: First-Line Short Courses
- Background
- Short courses for 3-4 months are preferred for Latent Tuberculosis management over traditional 6-9 month courses
- Similar efficacy as with Isoniazid 6-9 month monotherapy course
- Higher compliance and completion rates compared with longer courses
- Less hepatotoxicity compared with longer courses
- Isoniazid and Rifapentine for 3 months (3HP)
- Indications
- Preferred regimen for adults and children >2 years
- Also preferred in HIV positive patients (unless Rifampin Drug Interactions prohibit)
- Rifapentine has multiple Drug Interactions but less than with Rifampin
- Requires observed therapy (patient must come to clinic weekly for administered dose)
- Combination of both Isoniazid (INH) and Rifapentine both weekly for 12 weeks
- Each dose must be physician observed (due to risk of drug resistant Tuberculosis if stopped early)
- Protocol (Age >=2 years)
- Isoniazid (INH) 15 mg/kg (25 mg/kg if age 2-11 years) up to 900 mg weekly for 12 weeks AND
- Rifapentine (Priftin) weekly for 12 weeks
- Weight 10 to 14 kg: Rifapentine 300 mg weekly
- Weight 14.1 to 25 kg: Rifapentine 450 mg weekly
- Weight 2.5.1 32 kg: Rifapentine 600 mg weekly
- Weight 32.1 to 49.9 kg: Rifapentine 750 mg weekly
- Weight >50 kg (and adults): Rifapentine 900 mg weekly
- Efficacy: 90% effective
- As effective and safe as other Latent Tb regimens with significantly higher completion rates
- Njie (2018) Am J Prev Med 55(2):244-252 +PMID: 29910114 [PubMed]
- References
- Sterling (2011) N Engl J Med 365:2155-2166 [PubMed]
- Rifampin for 4 months (4R)
- Indications
- Short course self-administered monotherapy
- Cost may be prohibitive - very expensive (10-20 times the cost of Isoniazid)
- Contraindications
- Do not use as monotherapy in HIV Infection
- Review Drug Interactions before use (multiple rifampin Drug Interactions, but less with Rifabutin)
- Allows for shorter course and lower hepatotoxicity risk
- Rifampin Routine Dosing (intermittent dosing not recommended when used alone)
- Adults 10 mg/kg up to 600 mg orally daily for 4 months
- Child 10-20 mg/kg/day (max 600 mg/day) for 4 months
- Efficacy: 60% effective
- Not inferior to Isoniazid for 9 months, and better completion rates with less adverse effects
- Menzies (2018) N Engl J Med 379(5):440-53 +PMID: 30067931 [PubMed]
- Isoniazid and Rifampin for 3 months (3HR)
- Indications
- Adults and children of all ages including HIV positive patients
- Contraindications
- Rifampin Drug Interactions
- Protocol: Taken daily for 3 months
- Isoniazid (INH) 5 mg/kg in adults (10-20 mg/kg in children) up to 300 mg daily AND
- Rifampin 10 mg/kg in adults (15-20 mg/kg in children) up to 600 mg daily
- Protocols: Latent Tuberculosis Long Course Treatment
- See Isoniazid for specific precautions and Vitamin B6 supplementation guidelines
- Typical long course: 9 months (unless otherwise noted - see below)
- Course of 9 months is now also recommended in cases previously treated for 12 months
- Human Immunodeficiency Virus (HIV)
- Immunosuppression
- Chest XRay showing healed Tuberculosis (e.g. apical fibronodular changes)
- Protocol
- Duration
- Standard therapy: 9 months (90% effective)
- Shorter course: 6 months (60-80% effective, but better compliance)
- Isoniazid Routine Dosing
- Adults 5 mg/kg up to 300 mg orally daily
- Child 10-20 mg/kg/day (max 300 mg/day)
- Isoniazid Alternative Dosing
- Adult: 15 mg/kg up to 900 mg twice weekly supervised
- Child: 20-40 mg/kg twice weekly (maximum 900 mg) supervised
- Protocols: Resistant Exposures
- Isoniazid Resistant Tuberculosis Exposure
- Rifampin 600 mg qd
- Ethambutol for 6-12 months
- Multi-drug resistant Tb Exposure:
- Pyrazinamide 25-30 mg/kg/day and
- Ethambutol 15-25mg/kg/day and
- Fluoroquinolones
- Ofloxacin 400mg bid or
- Ciprofloxacin 750 mg bid
- Protocols: Discontinued - Rifampin and Pyrazinamide
- No longer recommended for Latent Tuberculosis Treatment due to hepatotoxicity
- Details listed for historical purposes only
- Rifampin 600 mg qd for 2 months
- Pyrazinamide 25mg/kg qd for 2 months
- Higher risk of hepatotoxicity than with 6 months INH
- Observe serial Liver Function Tests closely
- Jasmer (2002) Ann Intern Med 137:640-7 [PubMed]
- Monitoring
- See Isoniazid for toxicity related to Neuropathy and Hepatotoxicity
- See Rifampin regarding Drug Interactions
- Resources
- Treatment Regimens for Latent Tuberculosis or LTBI (CDC)
- https://www.cdc.gov/tb/topic/treatment/ltbi.htm
- References
- Orman, Moran and Swaminathan in Herbert (2016) EM:Rap 16(11): 2-3
- Hartman-Adams (2014) Am Fam Physician 89(11): 889-96 [PubMed]