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

Am J Respir Crit Care Med. 2000 May;161(5):1572-7. doi: 10.1164/ajrccm.161.5.9904090.


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 x 10(6) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antitubercular / administration & dosage*
  • Antitubercular Agents / administration & dosage
  • Colony Count, Microbial
  • Drug Administration Schedule
  • Drug Resistance, Microbial
  • Drug Therapy, Combination
  • Ethambutol / administration & dosage
  • Female
  • Isoniazid / administration & dosage
  • Lung / microbiology
  • Mice
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Pyrazinamide / administration & dosage
  • Rifampin / administration & dosage
  • Rifampin / analogs & derivatives*
  • Spleen / microbiology
  • Streptomycin / administration & dosage
  • Tuberculosis / drug therapy*
  • Tuberculosis / microbiology


  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Pyrazinamide
  • Ethambutol
  • Isoniazid
  • Rifampin
  • rifapentine
  • Streptomycin