Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1572-1577

Antituberculosis Activity of Once-weekly Rifapentine-containing Regimens in Mice
Long-term Effectiveness with 6- and 8-Month Treatment Regimens

NATHALIE DANIEL, NACER LOUNIS, BAOHONG JI, RICHARD J. O'BRIEN, ANDREW VERNON, LAWRENCE J. GEITER, MICHEL SZPYTMA, CHANTAL TRUFFOT-PERNOT, GILLES HEJBLUM, and JACQUES GROSSET

Faculté de Médecine Pitié-Salpêtrière, Paris, France; Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, Atlanta, Georgia; Sequella Global Tuberculosis Foundation, Rockville, Maryland; and Unité INSERM 494, Paris, France

The effectiveness of various once-weekly 10 mg/kg rifapentine (P)- containing regimens for treatment of tuberculosis was assessed in mice infected intravenously with 4.3 × 10⁶ colony-forming units (cfu) of Mycobacterium tuberculosis 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, respectively. Treatment failure with emergence of R-resistant bacilli occurred in all mice given once-weekly monotherapy with P for 6 mo. Once-weekly PH treatment was successful at 6 mo when it was preceded by a 2-mo daily phase 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 supplemented with S during the initial daily and the once-weekly phases, and at 8 mo if it was supplemented with daily H during the once-weekly phase. Without these supplements, once-weekly treatment failed in some mice with selection of R-resistant or H-resistant mutants.

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