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

Treatment of Latent Tuberculosis Infection

The preferred treatment regimens for latent tuberculosis infection (LTBI) include a 3-month once-weekly isoniazid plus rifapentine regimen, a 4-month daily rifampin regimen, or a 9-month daily isoniazid regimen, with selection based on patient factors and drug interactions. 1

First-Line Treatment Options

3-Month Once-Weekly Isoniazid plus Rifapentine (3HP)

• Strong recommendation with moderate to high quality evidence 1
• Requires directly observed therapy (DOT)
• Higher completion rates compared to 9-month isoniazid (82.1% vs 69.0%) 2
• Lower rates of hepatotoxicity (0.4%) compared to 9-month isoniazid (2.7%) 2
• May cause flu-like reactions more frequently than other regimens 3
• Careful evaluation of potential drug interactions required

4-Month Daily Rifampin (4R)

• Strong recommendation with moderate to high quality evidence 1
• Dosing: 10 mg/kg daily (not to exceed 600 mg/day) 4
• Higher completion rates and less hepatotoxicity than isoniazid 1, 5
• The 4-month rifampin regimen was not inferior to 9-month isoniazid for prevention of active TB in a large randomized trial 5
• Suitable for patients who cannot tolerate isoniazid 1
• Administered once daily, either 1 hour before or 2 hours after a meal with a full glass of water 4

9-Month Daily Isoniazid (9H)

• Strong recommendation with moderate quality evidence 1
• Provides >90% protection when completed properly 1
• Traditional standard of care but limited by toxicity and lower completion rates 1, 5

Special Populations

Children

• Children ≥2 years: Can receive rifapentine plus isoniazid with weight-based dosing 1
• Children <2 years: Should receive 9 months of isoniazid 1
• For pediatric patients with difficulty swallowing capsules, rifampin can be prepared as an oral suspension 4

Pregnant Women

• 9 months of isoniazid is recommended 1
• Maximum protective effect of over 90% if completed properly 1

HIV-Infected Persons

• Treatment indicated for positive TST (≥5 mm) 1
• Rifampin-based regimens should be used with caution due to potential drug interactions with antiretrovirals 1

Monitoring and Adverse Effects

Baseline Testing

• Liver function tests recommended for patients with risk factors:
  • HIV infection
  • Pregnancy or postpartum
  • Chronic liver disease
  • Regular alcohol use 1

During Treatment

• Monthly clinical evaluations for adverse effects, particularly hepatotoxicity 1
• Pyridoxine (vitamin B6) supplementation recommended for patients on isoniazid to prevent peripheral neuropathy 1

Rifampin-Specific Considerations

• Contraindications:
  • Known hypersensitivity to rifamycins
  • Concurrent use of certain antiretrovirals 1
• Induces hepatic microsomal enzymes, accelerating clearance of many medications:
  • Oral contraceptives
  • Anticoagulants
  • Corticosteroids
  • Oral hypoglycemic agents
  • Anticonvulsants
  • Methadone 1
• Colors body fluids orange (tears, sweat, urine)
• May permanently discolor soft contact lenses
• May reduce effectiveness of hormonal contraceptives 1

Critical Pitfalls to Avoid

1. Failing to rule out active TB before starting LTBI treatment

   • Must perform symptom screening, chest radiography, and collect sputum specimens if pulmonary symptoms are present 1
   • Starting LTBI treatment in patients with active TB can lead to drug resistance 1

2. Inadequate monitoring for hepatotoxicity

   • Particularly important with isoniazid regimens 1
   • Regular clinical evaluation is essential

3. Overlooking drug interactions with rifampin

   • Rifampin induces hepatic enzymes affecting many medications 1, 4
   • Verify compatibility with patient's current medications

4. Poor adherence management

   • Shorter regimens like 4-month rifampin have better completion rates than 9-month isoniazid 5, 6
   • Consider patient factors that may affect adherence when selecting a regimen

5. Adding a single drug to a failing regimen

   • Can promote further resistance
   • At least two new drugs should be added if treatment failure is suspected 1

By following these evidence-based recommendations and avoiding common pitfalls, clinicians can effectively treat latent TB infection and prevent progression to active disease.