What are the preferred treatments for latent tuberculosis (TB)?

Preferred Treatments for Latent Tuberculosis Infection

The preferred first-line treatment for latent TB is 3 months of once-weekly isoniazid plus rifapentine (3HP), which has equivalent efficacy to 9 months of isoniazid but achieves higher completion rates (82% vs 69%) and causes significantly less hepatotoxicity (0.4% vs 2.7%). 1, 2

First-Line Preferred Regimens

For HIV-Negative Adults and Children ≥2 Years

• 3 months of once-weekly isoniazid (900 mg) plus rifapentine (900 mg) administered as directly observed therapy (DOT) is the CDC's top recommendation, demonstrating non-inferiority to 9-month isoniazid with superior treatment completion and safety profiles 1, 3, 2

• 4 months of daily rifampin (4R) serves as the preferred alternative for all ages, showing clinical equivalence to 9-month isoniazid with lower toxicity and a 15.1 percentage point higher completion rate (79% vs 64%) 1, 4

For HIV-Positive Persons

• The 3HP regimen is equally effective in HIV-positive and HIV-negative persons and represents the preferred option 1

• If rifamycin-based regimens are contraindicated, use 9 months of daily isoniazid (9H), not 6 months, as the longer duration provides superior protection in this population 1

Alternative Regimens When First-Line Options Are Contraindicated

• 9 months of daily isoniazid provides 60-90% protective efficacy if completed, but should be reserved for situations where rifamycin-based regimens cannot be used 1

• Avoid 6 months of isoniazid in HIV-infected persons or those with radiographic evidence of prior TB, as it provides inferior protection compared to 9 months 1

Special Population Considerations

Pregnant Women

• For high-risk women (HIV-infected or recently infected), do not delay treatment based on pregnancy alone, even in the first trimester 1

• Isoniazid (9 or 6 months) is recommended for HIV-negative pregnant women 1

• Rifampin is not recommended during pregnancy 1

Children and Adolescents

• Short-course rifamycin-based regimens appear superior to 9 months of isoniazid in children, with better completion rates and comparable or better effectiveness 1, 5

• For children 2-11 years on 3HP: use isoniazid 25 mg/kg (maximum 900 mg) weekly 3

• For children ≥12 years on 3HP: use isoniazid 15 mg/kg (maximum 900 mg) weekly 3

Drug-Resistant Exposure

• Contacts of isoniazid-resistant, rifampin-susceptible TB: treat with 4 months of rifampin alone, or rifampin plus pyrazinamide for 2 months if pyrazinamide is tolerated 1

• Contacts of multidrug-resistant TB: use pyrazinamide plus ethambutol or pyrazinamide plus a fluoroquinolone for 6-12 months 1

Critical Pre-Treatment Requirements

Active TB disease must be ruled out before initiating latent TB treatment through:

• History and physical examination focusing on TB symptoms (cough, fever, night sweats, weight loss) 1

• Chest radiography 1

• Bacteriologic studies when clinically indicated 1

Monitoring During Treatment

Baseline Assessment

• Obtain baseline liver function tests for patients with suspected liver disorders, HIV infection, pregnancy or immediate postpartum period, or chronic conditions increasing liver disease risk 1

Ongoing Monitoring

• Monthly clinical evaluations for all patients on isoniazid or rifampin monotherapy, assessing for hepatitis symptoms 1

• For patients on rifampin plus pyrazinamide regimens: evaluate at 2,4, and 8 weeks 1

• Discontinue treatment immediately if evidence of liver injury occurs 1, 3

• For patients with abnormal baseline liver tests or liver disease receiving rifapentine, obtain serum transaminases every 2-4 weeks during therapy 3

Administration Details for 3HP Regimen

• Always administer with meals to increase bioavailability and reduce gastrointestinal side effects 3

• For patients unable to swallow tablets, crush and mix with semi-solid food, consuming immediately 3

• Weight-based dosing for rifapentine ranges from 300 mg (10-14 kg) to 900 mg (>50 kg) 3

Critical Pitfalls to Avoid

• Never use rifapentine as monotherapy for latent TB treatment 1, 3

• Never use 2-month rifampin-pyrazinamide (2RZ) in HIV-negative adults due to unacceptably high hepatotoxicity risk, despite its efficacy 1, 6

• Do not use once-weekly rifapentine-isoniazid for active TB treatment in HIV-infected patients due to higher failure rates and rifampin-resistant relapse 3

• Never add a single drug to a failing regimen; always add at least 2 drugs to which the organism is susceptible to prevent resistance 1

• Intermittent (twice-weekly) isoniazid regimens must always be administered as directly observed therapy 1

• Do not use 3HP in individuals presumed exposed to rifamycin-resistant or isoniazid-resistant M. tuberculosis 3