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, Jacques Grosset

Research output: Contribution to journalArticle

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)1572-1577
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume161
Issue number5
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Daniel, N., Lounis, N., Ji, B., O'Brien, R. J., Vernon, A., Geiter, L. J., Szpytma, M., Truffot-Pernot, C., Hejblum, G., & Grosset, J. (2000). Antituberculosis activity of once-weekly rifapentine-containing regimens in mice: Long-term effectiveness with 6- and 8-month treatment regimens. American journal of respiratory and critical care medicine, 161(5), 1572-1577. https://doi.org/10.1164/ajrccm.161.5.9904090