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

Treatment of Latent Tuberculosis Infection

The preferred regimens for 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 regimens have excellent efficacy and higher completion rates than longer regimens. 1

Preferred Regimens

• 3 months of once-weekly isoniazid plus rifapentine - This regimen is strongly recommended with moderate quality evidence. It has been shown to be as effective as 9 months of isoniazid alone in preventing tuberculosis while having higher treatment completion rates 1, 2

• 4 months of daily rifampin - This regimen is strongly recommended with moderate quality evidence for HIV-negative individuals. It has demonstrated non-inferiority to 9 months of isoniazid with better safety profiles and higher completion rates 1, 3

• 3 months of daily isoniazid plus rifampin - This regimen is conditionally recommended with very low quality evidence for HIV-negative individuals and low quality evidence for HIV-positive individuals 1

Alternative Regimens

• 6 months of daily isoniazid - This regimen is strongly recommended for HIV-negative adults and children and conditionally recommended for HIV-positive individuals 1

• 9 months of daily isoniazid - This regimen is conditionally recommended for all adults and children, both HIV-negative and HIV-positive 1

Special Considerations

HIV-Positive Individuals

• When isoniazid is chosen for treatment of LTBI in persons with HIV infection, 9 months rather than 6 months is recommended 1
• Isoniazid plus antiretroviral therapy decreases the incidence of TB disease to a greater extent than either isoniazid alone or antiretroviral therapy alone 1
• When rifampin cannot be used due to drug interactions with antiretroviral medications, rifabutin may be substituted 1, 4

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 due to pregnancy, even during the first trimester 1
• For women at lower risk, some experts recommend waiting until after delivery to start treatment 1

Children and Adolescents

• For children and adolescents, isoniazid given either daily or twice weekly for 9 months is the recommended regimen 1
• The 3-month once-weekly isoniazid plus rifapentine regimen is approved for children 2 years and older 4

Drug-Resistant TB Contacts

• For contacts of patients with isoniazid-resistant, rifampin-susceptible TB, rifampin given daily for 4 months is recommended 1
• For persons likely infected with isoniazid- and rifampin-resistant (multidrug-resistant) TB who are at high risk for developing TB, pyrazinamide and ethambutol or pyrazinamide and a quinolone for 6-12 months are recommended 1

Dosing Guidelines

For 3 months once-weekly isoniazid plus rifapentine:

• Adults and children 12 years and older: Rifapentine dose based on weight (maximum 900 mg once weekly) plus isoniazid 15 mg/kg (maximum 900 mg once weekly) 4
• Children 2-11 years: Rifapentine dose based on weight (maximum 900 mg once weekly) plus isoniazid 25 mg/kg (maximum 900 mg once weekly) 4

Monitoring and Safety Considerations

• Before beginning treatment of LTBI, active TB should be ruled out by history, physical examination, chest radiography, and bacteriologic studies when indicated 1
• Patients should receive follow-up evaluations at least monthly for isoniazid or rifampin monotherapy, and at 2,4, and 8 weeks for rifampin plus pyrazinamide regimens 1
• Baseline laboratory testing is not routinely indicated for all patients but should be considered for those with risk factors for hepatotoxicity 1
• Hepatotoxicity risk is higher with rifampin and pyrazinamide given together than with either drug alone 1
• Rifampin-based regimens have shown significantly less hepatotoxicity compared to isoniazid regimens 3, 5

Treatment Completion and Adherence

• Shorter regimens have demonstrated significantly higher completion rates compared to the 9-month isoniazid regimen 3, 2, 5
• The 3-month once-weekly isoniazid plus rifapentine regimen had a completion rate of 82.1% compared to 69.0% for the 9-month isoniazid regimen in one study 2
• When isoniazid is given intermittently (twice weekly), it should be administered only as directly observed therapy (DOT) 1

Potential Pitfalls and Caveats

• Drug interactions with rifamycins (rifampin, rifapentine, rifabutin) are common, particularly with warfarin, oral contraceptives, antifungals, and HIV antiretroviral therapy 1
• Rifapentine should be taken with meals to increase bioavailability and reduce gastrointestinal upset 4
• Rifampin and rifapentine should not be used in persons presumed to be exposed to rifamycin-resistant TB 4
• Patients on rifamycin-based regimens should be monitored for symptoms of liver injury, especially those with abnormal baseline liver tests or liver disease 4