Heddleston L, McDuffie R S, Gibbs R S
Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver 80262.
Am J Obstet Gynecol. 1993 Sep;169(3):708-12. doi: 10.1016/0002-9378(93)90647-2.
In a modified pregnant rabbit model using intracervical inoculation of Escherichia coli we investigated the effects of administration of delayed antibiotics and indomethacin on outcomes.
We inoculated 10(5) colony-forming units of Escherichia coli or saline solution bilaterally in the cervix of New Zealand White rabbits at 70% of gestation and assigned animals to ampicillin-sulbactam therapy beginning at 0, 4, 8, 12, and 16 hours after inoculation with Escherichia coli or to no antibiotic therapy. We alternated indomethacin pretreatment in rabbits receiving no antibiotic therapy and rabbits starting ampicillin-sulbactam 4 hours after inoculation.
Compared with saline solution inoculated control animals, those inoculated with Escherichia coli (and given no antibiotic therapy) had significant increases in fetal loss, fever, bleeding at 24 hours, and positive cultures (100%, 92%, 76%, 98% versus 0%, respectively, all p < 0.01). In Escherichia coli-inoculated animals receiving no antibiotic therapy pretreatment with indomethacin significantly decreased bleeding and delivery within first 24 hours compared with those not treated with indomethacin (p < 0.05) but did not significantly improve fetal survival. Ampicillin-sulbactam treatment stated at 0, 4, 8, and 12 hours after inoculation resulted in improved fetal survival compared with the untreated group (100%, 56%, 50%, 50% versus 0%, respectively, all p < 0.05). Treatment initiated at 16 hours resulted in outcomes similar to Escherichia coli-inoculated animals receiving no antibiotic therapy.
Intracervical Escherichia coli inoculation produced infection in the uterus and uniform pregnancy loss. Pretreatment with indomethacin did not result in improved fetal survival. Ampicillin-sulbactam therapy, initiated as long as 12 hours after Escherichia coli inoculation, resulted in significant improvement in fetal survival compared with antibiotic therapy. We believe this model mimics ascending infection in pregnancy more closely than do previous animal models.
在一种改良的孕兔模型中，通过宫颈内接种大肠杆菌，我们研究了延迟使用抗生素和吲哚美辛对结局的影响。
在妊娠70%时，我们向新西兰白兔的双侧宫颈内接种10⁵ 个菌落形成单位的大肠杆菌或生理盐水，并将动物分为在接种大肠杆菌后0、4、8、12和16小时开始接受氨苄西林-舒巴坦治疗组或不接受抗生素治疗组。我们在不接受抗生素治疗的兔子和接种大肠杆菌4小时后开始使用氨苄西林-舒巴坦的兔子中交替进行吲哚美辛预处理。
与接种生理盐水的对照动物相比，接种大肠杆菌（且未接受抗生素治疗）的动物在胎儿丢失、发热、24小时时出血以及培养阳性方面显著增加（分别为100%、92%、76%、98% 对0%，所有p < 0.01）。在接种大肠杆菌且未接受抗生素治疗的动物中，与未用吲哚美辛治疗的动物相比，吲哚美辛预处理显著减少了24小时内的出血和分娩（p < 0.05），但未显著提高胎儿存活率。与未治疗组相比，在接种后0、4、8和12小时开始的氨苄西林-舒巴坦治疗提高了胎儿存活率（分别为100%、56%、50%、50% 对0%，所有p < 0.05）。在16小时开始治疗导致的结局与接种大肠杆菌且未接受抗生素治疗的动物相似。
宫颈内接种大肠杆菌导致子宫感染和一致的妊娠丢失。吲哚美辛预处理未提高胎儿存活率。与不使用抗生素治疗相比，在接种大肠杆菌后长达12小时开始的氨苄西林-舒巴坦治疗显著提高了胎儿存活率。我们认为该模型比以前的动物模型更接近模拟妊娠中的上行感染。
