What is the treatment for latent tuberculosis (TB)?

Treatment of Latent Tuberculosis Infection

Short-course (3-4 month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of latent tuberculosis infection (LTBI). 1

Preferred Regimens

1. 3 months of once-weekly isoniazid plus rifapentine

   • Strong recommendation with moderate quality evidence 1
   • Administered as directly observed therapy (DOT) or self-administered therapy
   • Equivalent effectiveness to 9 months of isoniazid with less hepatotoxicity 1
   • Higher completion rates than longer regimens 1
   • Dosing based on weight (maximum 900 mg once weekly) 2

2. 4 months of daily rifampin

   • Strong recommendation with moderate quality evidence (for HIV-negative individuals) 1
   • Noninferior to 9 months of isoniazid for preventing active TB 3
   • Higher treatment completion rates and better safety profile 3
   • Lower rate of hepatotoxicity than isoniazid 1, 3

3. 3 months of daily isoniazid plus rifampin

   • Conditional recommendation with very low quality evidence (HIV-negative) 1
   • Conditional recommendation with low quality evidence (HIV-positive) 1
   • Similar effectiveness to 6 months of isoniazid 1
   • Safe and potentially superior to 9-month isoniazid monotherapy in children 4

Alternative Regimens

1. 6 months of daily isoniazid

   • Strong recommendation with moderate quality evidence (HIV-negative) 1
   • Conditional recommendation with moderate quality evidence (HIV-positive) 1
   • Substantial protection but less than the 9-month regimen 1

2. 9 months of daily isoniazid

   • Conditional recommendation with moderate quality evidence 1
   • Maximum protective effect of over 90% if completed properly 5
   • Higher risk of hepatotoxicity and lower completion rates than rifamycin-based regimens 1

Special Populations

HIV-Positive Individuals

• When using isoniazid for HIV-positive patients, 9 months is recommended rather than 6 months 1
• 3 months of once-weekly isoniazid plus rifapentine is effective 1
• Drug interactions between rifamycins and antiretroviral therapy must be carefully managed 1

Children

• For children and adolescents, all preferred regimens are appropriate 1
• Weight-based dosing for rifapentine in children 2 years and older 2
• 3-4 months of isoniazid plus rifampin has shown excellent safety and efficacy in children 4

Pregnant Women

• Isoniazid daily or twice weekly for 9 months is recommended 5
• For high-risk pregnant women (HIV-infected or recent exposure), treatment should not be delayed 1
• For lower-risk pregnant women, some experts recommend waiting until after delivery 5

Monitoring and Safety

Baseline Assessment

• Rule out active TB before starting LTBI treatment through history, physical examination, chest radiography, and when indicated, bacteriologic studies 1
• Baseline liver function tests are recommended for patients with risk factors (HIV infection, pregnancy, chronic liver disease, regular alcohol use) 5

Follow-up Monitoring

• Monthly clinical evaluations for patients on isoniazid or rifampin alone 1
• More frequent monitoring (at 2,4, and 8 weeks) for patients on rifampin and pyrazinamide 1
• Assessment should include questioning about side effects and brief physical examination for signs of hepatitis 1

Common Adverse Effects

• Hepatotoxicity: More common with isoniazid than with rifampin-based regimens 3
• Flu-like reactions: More common with rifapentine-containing regimens 6
• Drug interactions: Particularly significant with rifamycin-containing regimens 1

Important Considerations

• Rifampin and rifapentine are not interchangeable; care should be taken to ensure patients receive the correct medication for the intended regimen 1
• Pyridoxine (vitamin B6) supplementation should be added to reduce the risk of peripheral neuropathy in patients taking isoniazid 5
• Treatment completion is critical for effectiveness; shorter regimens generally have higher completion rates 1, 3
• The 2-month regimen of rifampin and pyrazinamide is no longer recommended for HIV-negative adults due to high rates of severe hepatotoxicity 1

Pitfalls to Avoid

• Failing to rule out active TB before starting LTBI treatment
• Not monitoring for hepatotoxicity, especially in high-risk patients
• Overlooking potential drug interactions with rifamycin-based regimens
• Confusing rifampin and rifapentine when prescribing
• Using shorter isoniazid regimens (6 months) in HIV-positive individuals when 9 months is recommended

By following these evidence-based guidelines for LTBI treatment, clinicians can effectively prevent progression to active TB while minimizing adverse effects and maximizing treatment completion.