Satranidazole: experimental evaluation of activity against anaerobic bacteria in vitro and in animal models of anaerobic infection

Abstract

Satranidazole, a 5-nitroimidazole derivative, was tested for its activity against reference strains and clinical isolates of anaerobic bacteria in vitro and in two murine models of anaerobic infection in comparison with metronidazole, tinidazole, ornidazole and clindamycin. The MIC90 of satranidazole against 50 clinical isolates of anaerobes was 0.25 mg/l which was four-fold lower than the MIC90 of metronidazole, tinidazole and ornidazole (MIC90 = 1.0 mg/l). In a fatal murine infection with Fusobacterium necrophorum, ATCC 27852, the ED50 of satranidazole was 2.1 +/- 0.62 mg/kg while for metronidazole, ornidazole, tinidazole and clindamycin, the values were 11.31 +/- 1.99, 8.70 +/- 2.21, 13.19 +/- 2.39 and 7.10 +/- 1.73 respectively. In a subcutaneous Bacteroides fragilis abscess in mice, satranidazole alone produced a three log reduction in cfu of the infecting organism at 10 mg/kg, the lowest dose tested. At 100 mg/kg, only satranidazole and clindamycin effected a complete sterilization of abscesses.