Public Health

Hepatotoxicity common with rifampin/pyrazinamide for latent TB

Last Updated: 2004-12-15 17:11:10 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Rifampin and pyrazinamide (RZ) treatment of latent tuberculosis infection carries an unacceptably high risk of hepatoxicity, even with intermittent dosing and careful monitoring, Tennessee researchers report.

The rate of hepatotoxicity in a group of patients with latent TB infection receiving RZ treatment was 69 cases per 1,000 people treated, Dr. David H. Priest of the Vanderbilt University School of Medicine in Nashville and colleagues report.

"A high margin of safety is needed for treatment of latent TB infection, because the risk of progression to tuberculosis is relatively low," they note in their report in the December 15th issue of Clinical Infectious Diseases.

In 2000, the American Thoracic Society and the Centers for Disease Control and Prevention recommended RZ twice weekly for 2 months for patients with latent TB who were not likely to complete treatment with isoniazid, which takes 6 to 9 months. This recommendation was based on studies of the regimen in HIV-infected individuals. But reports of severe hepatoxicity with RZ, mostly in HIV-negative people, soon appeared, and RZ for latent TB was no longer recommended.

The current study looked at a group of employees of a Tennessee food processing plant who underwent RZ treatment for latent TB. The employees, many of whom were recent immigrants from Latin America, received targeted tuberculin testing at hiring and every year thereafter. Those with latent TB were given directly observed preventive therapy with RZ, and underwent laboratory tests at baseline. After reports of hepatotoxicity of the drug combination, laboratory monitoring was increased to once monthly and then to biweekly.

Eighty-three percent of the 423 patients prescribed RZ completed treatment, and 29 developed hepatotoxicity. Fourteen had symptoms, and two required hospitalization.

While the findings show directly observed therapy can result in high completion rates, Dr. Priest and colleagues write, they confirm RZ's unacceptable toxicity for patients with latent disease.

The only remaining alternative to 9 months of isoniazid treatment for latent TB, Dr. Henry M. Blumberg of Emory University School of Medicine, Atlanta, notes in an accompanying editorial, is 4 months of rifampin alone. But data on the effectiveness of this shorter course approach are lacking, he adds.

Clin Infect Dis 2004;39:1764-1775.