Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice

J. Grosset, N. Lounis, C. Truffot-Pernot, R. J. O'Brien, M. C. Raviglione, B. Ji

Research output: Contribution to journalArticle

Abstract

The bactericidal activities of several once-weekly rifapentine (P)- containing combination regimens against Mycobacterium tuberculosis, and their ability to prevent the selection of rifampin (R)-resistant mutants, were compared with those of the standard six-times-weekly regimen consisting of R, isoniazid (H), and pyrazinamide (Z) in a mouse experiment. Mice were infected intravenously with 1.3 x 107 cfu of M. tuberculosis strain H37Rv, and 8 wk of treatment began on Day 14 after infection, when mice were randomly allocated to an untreated control group and nine treatment groups of 30 mice each. At the end of 8 wk of treatment, all the tested regimens showed promising bactericidal activities. Once-weekly P alone was less bactericidal than six-times-weekly R alone; likewise, the once-weekly P-containing combined regimens were less bactericidal than the six-times-weekly standard regimen. However, the difference in killing was about 1 log10, which represented only a fraction of the overall 4 log10 to 5 log10 magnitude of killing effects. The addition of streptomycin (5) improved the bactericidal effect of once-weekly PHZ, and the effect of once-weekly PHZS was further enhanced when it was preceded by 2 wk of daily HZS. The latter regimen achieved the same level of activity as the standard six-times-weekly regimen. All of the once-weekly P-containing combined regimens were able to prevent the selection of R-resistant mutants, whereas monotherapy with R or P selected resistant mutants in approximately 50% of animals.

Original languageEnglish (US)
Pages (from-to)1436-1440
Number of pages5
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume157
Issue number5 I
StatePublished - 1998
Externally publishedYes

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rifapentine
Tuberculosis
Mycobacterium tuberculosis
Pyrazinamide
Isoniazid
Streptomycin
Rifampin
Control Groups
Infection

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Grosset, J., Lounis, N., Truffot-Pernot, C., O'Brien, R. J., Raviglione, M. C., & Ji, B. (1998). Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice. American Journal of Respiratory and Critical Care Medicine, 157(5 I), 1436-1440.

Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice. / Grosset, J.; Lounis, N.; Truffot-Pernot, C.; O'Brien, R. J.; Raviglione, M. C.; Ji, B.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 157, No. 5 I, 1998, p. 1436-1440.

Research output: Contribution to journalArticle

Grosset, J, Lounis, N, Truffot-Pernot, C, O'Brien, RJ, Raviglione, MC & Ji, B 1998, 'Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice', American Journal of Respiratory and Critical Care Medicine, vol. 157, no. 5 I, pp. 1436-1440.
Grosset J, Lounis N, Truffot-Pernot C, O'Brien RJ, Raviglione MC, Ji B. Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice. American Journal of Respiratory and Critical Care Medicine. 1998;157(5 I):1436-1440.
Grosset, J. ; Lounis, N. ; Truffot-Pernot, C. ; O'Brien, R. J. ; Raviglione, M. C. ; Ji, B. / Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice. In: American Journal of Respiratory and Critical Care Medicine. 1998 ; Vol. 157, No. 5 I. pp. 1436-1440.
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