What is the treatment for latent tuberculosis (TB)?

Treatment of Latent Tuberculosis Infection

The preferred regimens for treating latent tuberculosis infection (LTBI) are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin, as these shorter rifamycin-based regimens have excellent efficacy with higher completion rates and better safety profiles than longer isoniazid monotherapy. 1, 2

Preferred Treatment Regimens

• 3 months of once-weekly isoniazid plus rifapentine (3HP):

  • Adults and children 12 years and older: Rifapentine dose based on weight (maximum 900 mg) plus isoniazid 15 mg/kg (maximum 900 mg) once weekly 2, 3
  • Children 2-11 years: Rifapentine dose based on weight (maximum 900 mg) plus isoniazid 25 mg/kg (maximum 900 mg) once weekly 2, 3
  • This regimen has shown similar efficacy to 9 months of isoniazid with higher completion rates (82.1% vs. 69.0%) 4

• 4 months of daily rifampin (4R):

  • Recommended for both HIV-negative and HIV-positive individuals 2
  • This regimen has demonstrated non-inferiority to 9 months of isoniazid with better safety profile and higher completion rates 5
  • Particularly useful for patients who cannot tolerate isoniazid or pyrazinamide 1

• 3 months of daily isoniazid plus rifampin (3HR):

  • Safe and effective alternative, particularly in children 6
  • Has shown equivalent effectiveness to 6 months of isoniazid in randomized trials 7

Alternative Regimens

• 6 months of daily isoniazid (6H):

  • Strongly recommended for HIV-negative adults and children 1, 2
  • Provides substantial protection but with higher toxicity risk than rifamycin-based regimens 1

• 9 months of daily isoniazid (9H):

  • Conditionally recommended for all adults and children 1, 2
  • Traditional standard regimen with >90% efficacy if completed properly 7
  • Associated with higher rates of hepatotoxicity and lower completion rates 4

Special Populations

HIV-Infected Individuals

• When isoniazid is chosen for treatment of LTBI in persons with HIV infection, 9 months rather than 6 months is recommended 1, 2
• Rifabutin may be substituted for rifampin when drug interactions with antiretroviral medications are a concern 1, 2
• Isoniazid plus antiretroviral therapy decreases TB disease incidence more than either treatment alone 2

Pregnant Women

• For pregnant, HIV-negative women, isoniazid given daily or twice weekly for 9 or 6 months is recommended 1
• For women at high risk for progression to TB disease (HIV-infected or recently infected), treatment should not be delayed based on pregnancy alone 1

Children and Adolescents

• For children and adolescents, isoniazid given daily or twice weekly for 9 months is the traditional recommended regimen 1
• Shorter rifamycin-based regimens are now preferred due to better completion rates 1, 2

Drug-Resistant TB Contacts

• For contacts of patients with isoniazid-resistant, rifampin-susceptible TB: rifampin and pyrazinamide daily for 2 months, or rifampin daily for 4 months if pyrazinamide is not tolerated 1
• For contacts of multidrug-resistant TB: consider pyrazinamide and ethambutol or pyrazinamide and a quinolone for 6-12 months 1

Monitoring and Safety

• Before initiating LTBI treatment, active TB must be ruled out through history, physical examination, chest radiography, and bacteriologic studies when indicated 1, 2
• Follow-up evaluations should occur at least monthly for patients on isoniazid or rifampin monotherapy 1, 2
• Baseline laboratory testing is recommended for patients with risk factors for hepatotoxicity 2
• Monitor for symptoms of liver injury, especially in patients with abnormal baseline liver tests or liver disease 2, 3
• Rifamycins have significant drug interactions, particularly with warfarin, oral contraceptives, antifungals, and HIV antiretroviral therapy 2

Administration Considerations

• Rifapentine should be taken with meals to increase bioavailability and reduce gastrointestinal upset 3
• For patients who cannot swallow tablets, rifapentine tablets may be crushed and added to a small amount of semi-solid food, which should be consumed immediately 3
• Directly observed therapy (DOT) is recommended for intermittent regimens to ensure adherence 1

Common Pitfalls

• Rifampin and rifapentine are not interchangeable; caution should be taken to ensure patients receive the correct medication for the intended regimen 1
• The 2-month regimen of rifampin plus pyrazinamide is no longer recommended due to risk of severe hepatotoxicity in non-HIV-infected adults 1, 7
• Failure to rule out active TB before starting LTBI treatment can lead to inadequate treatment and development of drug resistance 2, 3
• Inadequate monitoring for hepatotoxicity, especially in patients with risk factors, can lead to serious adverse events 2, 3