Safety and completion rate of short-course therapy for treatment of latent tuberculosis infection

Background. Nine months of isoniazid therapy is the recommended regimen for treatment of latent tuberculosis infection, but low completion rates are a serious problem. The search for shorter regimens, compared with the standard isoniazid regimen, is of vital importance. We describe our experience using short-course regimens for the treatment of latent tuberculosis infection. Methods. We conducted a nonrandomized, observational study of 459 patients in a county health department from June 2000 to January 2006. Short-course therapy was defined as pyrazinamide and rifampin taken daily or twice weekly for 2 months or rifampin taken daily for 4-6 months. Conventional therapy consisted of a 9-month regimen of isoniazid. Liver function testing was performed for both groups in accordance with clinical guidelines. Treatment completion and hepatotoxicity (according to the World Health Organization classification) were determined for the short-course and conventional therapy groups. Results. Treatment was completed by 241 (77.7%) of 310 patients in the short-course group and by 98 (65.8%) of 149 patients in the isoniazid group (P = .009). Moderate to severe hepatotoxicity (grades 3 and 4) occurred Pp. 009 in 6.1% of patients receiving short-course therapy and in 2.0% of patients receiving isoniazid (P = .09). The hepatotoxicity observed in the short-course group was confined to patients receiving pyrazinamide and rifampin daily and was self limited in all cases after the medications were discontinued. Conclusions. The rate of treatment completion was significantly higher with short-course regimens, compared with the isoniazid regimen. Although the overall risk of hepatotoxicity in patients receiving pyrazinamide and rifampin daily for the treatment of latent tuberculosis infection was higher, liver functions returned to normal after the medications were discontinued.