Antituberculosis activity of once-weekly rifapentine-containing regimens in mice - Long-term effectiveness with 6-and 8-month treatment regimens

The effectiveness of various once-weekly 10 mg/kg rifapentine (P)-containin g regimens for treatment of tuberculosis was assessed in mice infected intr avenously with 4.3 x 10(6) colony-forming units (du) of Mycobacterium tuber culosis H37Rv, and treated 14 d later with various combinations of rifampin (R), P, isoniazid (H), pyrazinamide (Z), ethambutol (E), or streptomycin ( S). Control mice treated daily with either 2-mo HRZ + 4-mo HR or 2-mo HRZ 6-mo HE were rendered spleen and lung culture-negative at 6 mo and 8 mo, r espectively. Treatment failure with emergence of R-resistant bacilli occurr ed in all mice given once-weekly monotherapy with P for 6 mo. Once-weekly P H treatment was successful at 6 mo when it was preceded by a 2-mo daily pha se with HRZ. When the initial daily phase was reduced to 2 wk, once-weekly PH-containing treatment was successful, at 6 mo, only if it was supplemente d with S during the initial daily and the once-weekly phases, and at 8 mo i f it was supplemented with daily H during the once-weekly phase. Without th ese supplements, once-weekly treatment failed in some mice with selection o f R-resistant or H-resistant mutants.