Activity in vitro of rifabutin, FCE 22807, rifapentine, and rifampin against Mycobacterium microti and M. tuberculosis and their penetration into mouse peritoneal macrophages.
The activities of the rifamycins, rifabutin, FCE 22807, rifapentine, and rifampin, were studied within unstimulated peritoneal macrophages infected with Mycobacterium microti and in cultures of M. microti and M. tuberculosis in 7H-9 medium without Tween 80. In macrophage cultures, serial rifamycin concentrations were added after a 2.5 h phagocytosis period, and viable counts were done after incubation for 5 to 6 days. To ensure comparability with the daily drug replacements in the macrophage experiments, the period of exposure to serial rifamycin concentrations in 7H-9 medium was kept to only 3 days. The MICs of M. microti and M. tuberculosis were similar. The MICs of rifabutin and FCE 22807 were 2.5 times lower and that of rifapentine 1.7 times lower than the MIC of rifampin. None of the rifamycins were concentrated in macrophages, the MICs being higher in the macrophages than in vitro by a factor of 2-fold for rifabutin, 6.7-fold for rifampin, 20-fold for FCE 22807, and 26-fold for rifapentine.
Dhillon
J
J
Department of Bacteriology, Royal Postgraduate Medical School, London, United Kingdom.
Mitchison
D A
DA
D000818:Animals; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology*; D017828:Rifabutin; D012293:Rifampin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D012294:Rifamycins / Q000493:pharmacokinetics / Q000494:pharmacology*
D000995:Antitubercular Agents; D012294:Rifamycins; D017828:Rifabutin; C065869:FCE 22807; D012293:Rifampin; C018421:rifapentine