Rifapentine microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Microbiology
Mechanism of Action
Rifapentine, a cyclopentyl rifamycin, inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis but not in mammalian cells. At therapeutic levels, rifapentine exhibits bactericidal activity against both intracellular and extracellular M. tuberculosis organisms. Both rifapentine and the 25-desacetyl metabolite accumulate in human monocyte-derived macrophages with intracellular/extracellular ratios of approximately 24:1 and 7:1, respectively.
In Vitro Activity
Rifapentine and its 25-desacetyl metabolite have demonstrated in vitro activity against rifamycin-susceptible strains of Mycobacterium tuberculosis including cidal activity against phagocytized M. tuberculosis organisms grown in activated human macrophages.
The correlation between rifapentine MICs and clinical cure has not been established. Interpretive criteria/breakpoints to determine whether clinical isolates of M. tuberculosis are susceptible or resistant to rifapentine have not been established.
In Vivo Activity
In mouse infection studies a therapeutic effect, in terms of enhanced survival time or reduction of organ bioburden, has been observed in M. tuberculosis-infected animals treated with various intermittent rifapentine containing regimens. Animal studies have shown that the activity of rifapentine is influenced by dose and frequency of administration.
Drug Resistance
In the treatment of tuberculosis, a small number of resistant cells present within large populations of susceptible cells can rapidly become predominant. Rifapentine resistance development in M. tuberculosis strains is principally due to one of several single point mutations that occur in the rpoB portion of the gene coding for the beta subunit of the DNA-dependent RNA polymerase. The incidence of rifapentine resistant mutants in an otherwise susceptible population of M. tuberculosis strains is approximately one in 107 to 108 bacilli.
Cross Resistance
M. tuberculosis organisms resistant to other rifamycins are likely to be resistant to rifapentine. A high level of cross-resistance between rifampin and rifapentine has been demonstrated with M. tuberculosis strains. Cross-resistance does not appear between rifapentine and non-rifamycin antimycobacterial agents.[1]
References
Adapted from the FDA Package Insert.