What is the follow-up protocol for Latent Tuberculosis (TB) infection?

From the Guidelines

For latent tuberculosis follow-up, short-course rifamycin-based treatment regimens are preferred over longer-course isoniazid monotherapy, and patients should be monitored regularly during treatment to ensure completion of the prescribed regimen and to check for medication side effects. The recommended treatment options include short-course (3–4 months) rifamycin-based treatment regimens, as stated in the guidelines from the National Tuberculosis Controllers Association and CDC, 2020 1.

Key Considerations for Follow-up

• Monthly visits for clinical assessment and liver function tests are crucial, especially for those on isoniazid or rifampin-based regimens.
• Healthcare providers should assess medication adherence, monitor for adverse effects such as hepatotoxicity, peripheral neuropathy, and rash, and provide patient education about symptoms that warrant immediate medical attention.
• After completing treatment, no routine follow-up is typically required unless symptoms of active TB develop.

Treatment Options

• Short-course (3–4 months) rifamycin-based treatment regimens are preferred over the longer-course (6–9 months) isoniazid monotherapy for treatment of LTBI, as recommended by the guidelines from the National Tuberculosis Controllers Association and CDC, 2020 1.
• The shorter 3-month regimen of weekly isoniazid plus rifapentine (3HP) is also an option.
• Rifampin 600mg daily for 4 months is another treatment option.

Importance of Follow-up

Proper treatment of latent TB infection significantly reduces the risk of progression to active tuberculosis disease, which is both more difficult to treat and potentially transmissible to others. Regular follow-up and monitoring are essential to ensure the patient completes the treatment regimen and to promptly address any side effects or concerns, as emphasized in the guidelines from the American Thoracic Society 1.

From the FDA Drug Label

Isoniazid is recommended as preventive therapy for the following groups, regardless of age. Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy. Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of isoniazid or 4 months of isoniazid and rifampin, concomitantly.

The follow-up for latent tuberculosis typically involves 12 months of isoniazid therapy for certain groups, including those with HIV infection, fibrotic pulmonary lesions, or pulmonary silicosis, as well as 4 months of isoniazid and rifampin concomitantly for some cases 2.

• Key factors to consider in follow-up include:
  • Duration of therapy: 12 months for certain groups
  • Concomitant medications: rifampin may be used in combination with isoniazid for some cases
  • Risk factors: HIV infection, fibrotic pulmonary lesions, pulmonary silicosis, and other medical conditions that increase the risk of tuberculosis.

From the Research

Latent Tuberculosis Follow-up

• Latent tuberculosis infection (LTBI) treatment regimens include once-weekly isoniazid plus rifapentine for 3 months, daily rifampin for 4 months, daily isoniazid plus rifampin for 3-4 months, and daily isoniazid for 6-9 months 3
• Isoniazid monotherapy is efficacious in preventing TB disease, but the rifampin- and rifapentine-containing regimens are shorter and have similar efficacy, adequate safety, and higher treatment completion rates 3
• A 4-month rifampin regimen has been shown to have fewer serious adverse events and better adherence than 9 months of isoniazid 4
• A meta-analysis of published studies suggested that 4-month rifampin therapy was associated with a significant reduction in the risk of noncompletion and hepatotoxicity compared to 9-month isoniazid therapy 5

Treatment Regimens

• 9 months of daily self-administered isoniazid (9H) has an efficacy of more than 90% if completed properly, but is associated with serious adverse events, including hepatotoxicity 6
• 2 months of rifampin and pyrazinamide has excellent efficacy in experimental studies in mice and randomized trials, but is associated with an unacceptably high rate of severe liver toxicity in non-HIV-infected adults 6
• 3 to 4 months of INH and rifampin has equivalent effectiveness as 6 months INH in several randomized trials, but completion of therapy and toxicity has been the same as with INH 6
• 4 months of rifampin has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity 6, 4, 5

Adverse Events

• Grade 3 or 4 hepatotoxicity occurred in 16 of 422 isoniazid recipients compared with 3 of 418 rifampin recipients, with a risk difference of -3.1% (CI, -5% to -1%) 4
• Rates of hepatotoxicity were lower for patients who received 4-month rifampin therapy (range, 0%-0.7%), compared with the corresponding rates for patients who received 9-month isoniazid therapy (range, 1.4%-5.2%) 5
• A 2-month regimen of rifampin and pyrazinamide was associated with an increased risk for grade 3 or 4 hepatotoxicity compared with a 6-month regimen of isoniazid 7