Safety of 2 months of rifampin and pyrazinamide for treatment of latent tuberculosis

An alternative regimen for the treatment of latent tuberculosis infection is 2 months of rifampin and pyrazinamide, but some patients have died of hepatitis associated with this therapy. One hundred fourteen patients received rifampin/pyrazinamide in Wake County, North Carolina, between December 1999 and May 2002; 60.5% of these patients were homeless, and at least 17% drank alcohol to excess. Seventy-seven patients (67.5%) completed a full 2-month course. Nine patients had a history of viral hepatitis or chronic liver disease. Four of 114 (3.5%; 95% confidence interval, 1.0-8.7%) patients developed hepatitis on therapy, and another two had symptoms consistent with hepatitis but did not report for laboratory testing (total confirmed plus suspected hepatitis rate 5.3%; 95% confidence interval, 2.0-11.1%). No patient who developed hepatitis had a history of viral hepatitis or liver disease, and none had been previously treated with isoniazid. No patients died or were hospitalized due to drug side effects. Rifampin/pyrazinamide was associated with a significantly higher rate of hepatitis than previously described with isoniazid therapy for latent tuberculosis but resulted in a high completion rate. The rifampin/pyrazinamide regimen for latent tuberculosis infection may be useful for high-risk, traditionally nonadherent patient groups, but careful monitoring for toxicity is required.