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

Recommended Treatment for Latent Tuberculosis Infection

The recommended treatment for latent tuberculosis infection (LTBI) is a 3-month once-weekly regimen of isoniazid plus rifapentine, which offers excellent efficacy with higher completion rates and less hepatotoxicity than traditional regimens. 1

First-line Treatment Options

3-Month Once-Weekly Isoniazid Plus Rifapentine

• Preferred regimen for patients ≥2 years of age
• 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 1, 2
  • Children 2-11 years: Rifapentine (weight-based, maximum 900 mg) plus isoniazid 25 mg/kg (maximum 900 mg) once weekly for 12 weeks 2
• Advantages: Higher completion rates, shorter duration, less hepatotoxicity 1, 3
• Requires directly observed therapy (DOT) 1, 2
• Take with food to increase bioavailability and reduce gastrointestinal upset 2

9-Month Daily Isoniazid

• Traditional gold standard regimen
• Provides >90% protection when completed adequately 1
• Dosing: Daily self-administered therapy or twice-weekly directly observed therapy
• Disadvantages: Lower completion rates, higher risk of hepatotoxicity 1, 4

4-Month Daily Rifampin

• Alternative when isoniazid cannot be tolerated or isoniazid resistance is suspected
• Higher completion rates and less hepatotoxicity than isoniazid 1, 4
• Particularly useful for patients with risk factors for hepatotoxicity

3-4 Month Isoniazid Plus Rifampin

• Comparable efficacy to 9-month isoniazid
• Better completion rates in children 1

Monitoring and Adverse Effects

Hepatotoxicity

• Rifapentine plus isoniazid: Lower rates of hepatotoxicity (0.4%) compared to isoniazid alone (2.7%) 3
• Monthly clinical evaluations recommended to assess adherence and adverse effects 1
• Baseline liver function tests only recommended for patients with risk factors (HIV infection, liver disorders, etc.) 1
• Discontinue treatment if evidence of liver injury occurs 2

Hypersensitivity Reactions

• Flu-like reactions more common with rifapentine-containing regimens 5
• Discontinue treatment if signs of hypersensitivity occur 2

Other Considerations

• Rifamycins may permanently stain contact lenses or dentures red-orange 2
• Pyridoxine (vitamin B6) supplementation recommended for certain patients (breastfeeding infants, those with diets likely deficient in pyridoxine, patients experiencing paresthesias) 1

Special Populations

Children

• Children under 5 years have higher risk of progression to active TB if untreated 1
• Children generally tolerate isoniazid better than adults with minimal risk of hepatotoxicity 1
• For children 2-11 years, 3-month once-weekly isoniazid plus rifapentine is recommended 1, 2

HIV-Infected Persons

• HIV-infected persons with positive TST (≥5 mm) should receive treatment for LTBI 1
• 3-month once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin have shown similar efficacy to 6 months of isoniazid in high TB incidence settings 6
• Caution with drug interactions between rifamycins and antiretroviral medications 2

Common Pitfalls to Avoid

• Confusing LTBI with active TB - active TB must be ruled out before starting LTBI treatment 1, 2
• Adding a single drug to a failing regimen, which can promote drug resistance 1
• Inadequate monitoring for hepatotoxicity, particularly with isoniazid regimens 1
• Overlooking drug interactions with rifampin-containing regimens 1
• Using rifapentine plus isoniazid in individuals presumed to be exposed to rifamycin-resistant or isoniazid-resistant M. tuberculosis 2