McDuffie R S, Heddleston L N, Blanton S J, Gibbs R S
Department of Obstetrics and Gynecology, Kaiser Permanente and Saint Joseph Hospital, Denver, Colorado, USA.
J Soc Gynecol Investig. 1995 Jan-Feb;2(1):23-5.
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.
Timed pregnant rabbits on day 21 (70% of gestation) were inoculated intracervically with 10(4)-10(5) 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.
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.
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.
比较标准剂量的氨曲南与两种庆大霉素剂量在早期治疗经宫颈接种大肠杆菌诱导的兔实验性羊膜腔内感染中的效果。
在妊娠第21天（妊娠期的70%）的定时妊娠兔经宫颈接种10⁴ - 10⁵ 个大肠杆菌菌落形成单位。接种后，动物接受三种治疗方案之一：1）氨曲南90 mg/kg/天（人类“标准”剂量），2）庆大霉素4.5 mg/kg/天（人类“标准”剂量），或3）高剂量庆大霉素6.0 mg/kg/天，均每日分三次给药。观察指标包括发热、分娩和活胎情况。尸检时，从子宫内膜、羊水和血液中取样培养。由于预期细胞大小少于5个，数据采用Fisher精确检验进行分析。
与接受氨曲南治疗的兔相比，接受4.5 mg/kg/天庆大霉素治疗的兔分娩频率显著更高（P = 0.002），培养阳性率更高（P < 0.001），活胎数量显著更少（P < 0.001）。与接受6.0 mg/kg/天庆大霉素治疗的兔相比，接受4.5 mg/kg/天庆大霉素治疗的兔分娩更频繁（P = 0.003），活胎数量更少（P = 0.02），培养阳性率更高（P = 0.02）。氨曲南组与6.0 mg/kg/天庆大霉素组之间无显著差异。
本研究在动物模型中表明，在早期治疗兔实验性羊膜腔内感染时，氨曲南和6.0 mg/kg/天的庆大霉素比4.5 mg/kg/天的庆大霉素（一种在人类中经验性广泛使用的剂量）更有效。氨曲南与6.0 mg/kg/天的庆大霉素效果相当。在这个羊膜腔内感染伴有母体败血症的兔模型中，4.5 mg/kg/天的庆大霉素不足以治疗严重的母体感染。
