What is the recommended treatment for latent tuberculosis (TB) infection?

Treatment of Latent Tuberculosis Infection

The preferred regimens for latent tuberculosis infection (LTBI) treatment are 3 months of once-weekly isoniazid plus rifapentine or 4 months of daily rifampin, as they offer excellent efficacy with shorter duration and better completion rates than traditional 9-month isoniazid regimens. 1, 2

Preferred Treatment Regimens

1. Three Months of Once-Weekly Isoniazid plus Rifapentine

• Strongly recommended by CDC and ATS for HIV-negative and HIV-positive adults and children ≥2 years old 1
• Dosing:
  • Adults and children ≥12 years: Rifapentine (weight-based, maximum 900 mg) plus isoniazid 15 mg/kg (maximum 900 mg) once weekly for 12 weeks 3
  • Children 2-11 years: Rifapentine (weight-based, maximum 900 mg) plus isoniazid 25 mg/kg (maximum 900 mg) once weekly for 12 weeks 3
• Advantages:
  • Shorter duration improves completion rates
  • Equivalent effectiveness to 9 months of isoniazid
  • Less hepatotoxicity than 9 months of isoniazid 1
• Disadvantages:
  • Higher medication costs
  • Potential systemic drug reactions (self-limited but can include syncope/hypotension)
  • Multiple pills taken simultaneously
  • Drug interactions with antiretrovirals and other medications 1

2. Four Months of Daily Rifampin

• Strongly recommended for HIV-negative adults and children of all ages 1
• Advantages:
  • Higher completion rates than 9 months of isoniazid
  • Lower rates of hepatotoxicity
  • Fewer pills than combination regimens 1
• Disadvantages:
  • Many drug interactions (warfarin, oral contraceptives, azole antifungals, HIV antiretrovirals)
  • No evidence for effectiveness in HIV-positive persons 1
  • Potential for acquired drug resistance if active TB not properly excluded 1

Alternative Treatment Regimens

1. Three Months of Daily Isoniazid plus Rifampin

• Conditionally recommended for both HIV-negative and HIV-positive individuals 1
• Similar effectiveness to 6+ months of isoniazid
• Higher completion rates than longer isoniazid regimens 1

2. Six or Nine Months of Daily Isoniazid

• Six months: Strong recommendation for HIV-negative, conditional for HIV-positive 1
• Nine months: Conditional recommendation for all patients 1
• Provides maximum protection of >90% if completed properly 2
• Disadvantages:
  • Lower completion rates due to longer duration
  • Risk of hepatotoxicity
  • Need for monthly monitoring 2

Monitoring During Treatment

1. Baseline Assessment

   • Rule out active TB before starting LTBI treatment 3
   • Baseline liver function tests for patients with risk factors:
     • Pregnancy or postpartum period
     • HIV infection
     • Chronic liver disease
     • Regular alcohol use 2

2. Ongoing Monitoring

   • Monthly clinical evaluations for all patients to assess:
     • Adherence
     • Signs of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice)
     • Other adverse effects (peripheral neuropathy with isoniazid) 2
   • Discontinue treatment if evidence of liver injury occurs 3

3. Supplementation

   • Add pyridoxine (vitamin B6) for patients on isoniazid to reduce risk of peripheral neuropathy 2

Special Considerations

1. HIV Co-infection

   • Three months of once-weekly isoniazid plus rifapentine is effective
   • Avoid rifampin-based regimens when certain antiretrovirals are used due to drug interactions
   • Do not use once-weekly isoniazid plus rifapentine in the continuation phase for active TB in HIV-positive patients due to higher relapse rates 1, 3

2. Pregnancy

   • Nine months of isoniazid is recommended for pregnant women with LTBI
   • Treatment may be initiated during pregnancy for high-risk individuals (HIV-infected or recent TB exposure) 2

3. Drug Interactions

   • Rifamycins have significant interactions with many medications
   • Rifabutin may be used in place of rifampin when drug interactions are a concern 1
   • Weekly rifapentine has fewer drug interactions than daily rifampin 1

Common Pitfalls to Avoid

1. Failing to rule out active TB before starting LTBI treatment
2. Poor adherence monitoring, resulting in incomplete treatment
3. Inadequate monitoring for hepatotoxicity, especially with isoniazid
4. Overlooking drug interactions with rifamycin-containing regimens
5. Using shorter regimens in situations where they're contraindicated (e.g., presumed exposure to drug-resistant TB) 2, 3

By selecting one of the preferred shorter regimens (3 months of isoniazid plus rifapentine or 4 months of rifampin), providers can maximize treatment completion while maintaining excellent efficacy for preventing progression to active TB disease.