Tuberculosis

Posted by Sara Fazio • December 9th, 2011

Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In a new study, 3 months of weekly isoniazid plus rifapentine (12 doses) was found to be noninferior to 9 months of isoniazid alone.

Tuberculosis results in nearly 2 million deaths annually worldwide. Treatment of latent Mycobacterium tuberculosis infection among persons at highest risk for progression to active infection is an important strategy for tuberculosis control and elimination.

Clinical Pearls

What are the limitations of the current standard of care for the treatment of latent tuberculosis?

The current standard regimen for the treatment of latent M. tuberculosis infection is 9 months of daily isoniazid. However, the effectiveness of isoniazid is limited by treatment completion rates of 30 to 64%, owing in part to the long duration of the regimen. Toxic effects of the drug, especially hepatic, are also a concern.

What new regimen is effective for the treatment of latent tuberculosis?

This study showed that for the treatment of latent M. tuberculosis, directly observed, once-weekly therapy with rifapentine plus isoniazid for 3 months was as effective as self-administered daily isoniazid for 9 months, with the rate of tuberculosis in the combination-therapy group approximately half that in the isoniazid-only group.

Morning Report Questions

Q: Which patients are at highest risk of conversion from latent M. tuberculosis infection to active disease?

A: Persons at high risk of conversion from latent tuberculosis to active disease include close contacts of a patient with culture-confirmed tuberculosis, a recent conversion to a positive tuberculin skin test (PPD), immunocompromised patients with a positive PPD, as well as patients with a positive PPD who have fibrotic changes on chest radiography consistent with previously untreated tuberculosis.

Q: What adverse effects were more common in the combination-therapy group (rifixamin plus isoniazid) than in the isoniazid-only group?

A: Among other adverse events attributed to study drug, the proportion of participants with possible hypersensitivity or other causes was higher in the combination-therapy group. The proportion of participants who permanently discontinued a study drug because of possible hypersensitivity was 2.9% in the combination-therapy group and 0.4% in the isoniazid-only group (P<0.001).

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