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

Treatment Regimens for Latent Tuberculosis Infection

The recommended treatment regimens for latent tuberculosis infection (LTBI) include 3 months of once-weekly isoniazid plus rifapentine or 4 months of daily rifampin as preferred options due to their excellent efficacy, shorter duration, and better completion rates compared to traditional 9-month isoniazid regimens. 1

Recommended Treatment Options

First-Line Regimens (in order of preference)

1. 3 months of once-weekly isoniazid plus rifapentine (3HP)

   • Administered as directly observed therapy (DOT)
   • Dosing:
     • Adults and children ≥12 years: Rifapentine dosed by weight (maximum 900 mg) plus isoniazid 15 mg/kg (maximum 900 mg) 1, 2
     • Children 2-11 years: Rifapentine dosed by weight (maximum 900 mg) plus isoniazid 25 mg/kg (maximum 900 mg) 2
   • Advantages: Excellent completion rates, fewer doses, less hepatotoxicity 1

2. 4 months of daily rifampin (4R)

   • Suitable for patients who cannot tolerate isoniazid
   • Advantages: Higher completion rates and less hepatotoxicity than isoniazid 1, 3
   • Caution: Significant drug interactions with many medications 1

3. 9 months of daily isoniazid (9H)

   • Maximum protective effect of over 90% if completed properly 1
   • Disadvantages: Longer duration, higher risk of hepatotoxicity, lower completion rates 4
   • Pyridoxine (vitamin B6) supplementation recommended to reduce risk of peripheral neuropathy 1

4. 6 months of daily isoniazid (6H)

   • Provides substantial protection but less than the 9-month regimen 1
   • May be more cost-effective in some settings 1

Special Populations

HIV Co-infection

• 3 months of once-weekly isoniazid plus rifapentine is effective 1
• Avoid rifampin-based regimens when certain antiretrovirals are used due to drug interactions 1
• HIV-infected persons with positive TST (≥5 mm) should receive treatment for LTBI 1

Pregnancy

• 9 months of isoniazid is recommended for pregnant women with LTBI 1
• Treatment may be initiated during pregnancy for high-risk individuals (HIV-infected or recent TB exposure) 1

Children

• Children 2 years and older can receive rifapentine plus isoniazid (weight-based dosing) 2
• For children under 2 years, 9 months of isoniazid is the recommended regimen 1

Monitoring During Treatment

1. Baseline Assessment

   • Rule out active TB disease before starting LTBI treatment 2
   • Chest radiography should be performed before LTBI treatment 5
   • Baseline liver function tests for patients with risk factors (pregnancy, HIV infection, chronic liver disease, regular alcohol use) 1

2. During Treatment

   • Monthly clinical evaluations for patients on isoniazid or rifampin to monitor for side effects 1
   • Monitor for hepatotoxicity, particularly with isoniazid and pyrazinamide regimens 1
   • Withhold isoniazid if transaminase levels exceed three times the upper limit of normal with symptoms or five times if asymptomatic 5

High-Risk Individuals Requiring LTBI Treatment

The World Health Organization strongly recommends systematic testing and treatment of LTBI in:

• People living with HIV
• Adult and child contacts of pulmonary TB cases
• Patients initiating anti-TNF treatment
• Patients receiving dialysis
• Patients preparing for organ transplantation
• Patients with silicosis 5

Conditional recommendations for testing and treatment in:

• Prisoners
• Healthcare workers
• Immigrants from high TB burden countries
• Homeless persons
• Illicit drug users 5

Potential Pitfalls to Avoid

1. Failing to rule out active TB before starting LTBI treatment, which can lead to drug resistance 1, 2
2. Poor adherence monitoring resulting in incomplete treatment and reduced effectiveness 1
3. Inadequate side effect monitoring, particularly for hepatotoxicity 1
4. Overlooking drug interactions with rifampin-containing regimens 1
5. Using single-drug regimens in patients with suspected exposure to drug-resistant TB 2

By following these evidence-based guidelines for LTBI treatment, clinicians can significantly reduce the risk of progression to active TB disease, thereby decreasing morbidity and mortality associated with tuberculosis.