Objective:To compare aztreonam in a standard dose with two gentamicin doses in the early treatment of experimental intra-amniotic infection in rabbits induced by intracervical inoculation with Escherichia coli.Methods:Timed pregnant rabbits on day 21 (70% of gestation) were inoculated intracervically with 10⁴-10⁵ colony-forming units of E coli. After inoculation, the animals were treated with one of three regimens: 1) aztreonam at 90 mg/kg/day (“standard” dose in humans), 2) gentamicin at 4.5 mg/kg/day (“standard” dose in humans), or 3) higher-dose gentamicin at 6.0 mg/kg/day, each given in three divided doses daily. Outcomes included fever, delivery, and presence of a live fetus. At necropsy, cultures were taken from endometrium, amniotic fluid, and blood. Data were analyzed by Fisher exact test because the expected cell size was fewer than five.Results:Compared with rabbits treated with aztreonam, those treated with gentamicin 4.5 mg/kg/day delivered significantly more often (P = .002), had more positive cultures (P < .001), and had significantly fewer live fetuses (P < .001). Compared with rabbits treated with gentamicin 6.0 mg/kg/day, those treated with gentamicin 4.5 mg/kg/day delivered more often (P = .003), had fewer live fetuses (P = .02), and had more positive cultures (P = .02). There were no significant differences between the aztreonam and gentamicin 6.0 mg/kg/day groups.Conclusions:This study demonstrates in an animal model that aztreonam and gentamicin at 6.0 mg/kg/day are more effective than gentamicin at 4.5 mg/kg/day (a dose that is widely used empirically in humans) in the early treatment of experimental intra-amniotic infection in rabbits. Aztreonam was as effective as gentamicin at 6.0 mg/kg/day. In this rabbit model, in which intra-amniotic infection is accompanied by maternal sepsis, 4.5 mg/kg/day of gentamicin was not adequate for the treatment of severe maternal infection.