A RABBIT MODEL FOR ASCENDING INFECTION IN PREGNANCY - INTERVENTION WITH INDOMETHACIN AND DELAYED AMPICILLIN-SULBACTAM THERAPY

OBJECTIVE: In a modified pregnant rabbit model using intracervical ino culation of Escherichia coli we investigated the effects of administra tion of delayed antibiotics and indomethacin on outcomes. STUDY DESIGN : We inoculated 10(5) colony-forming units of Escherichia coli or sali ne 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 Escheric hia coli or to no antibiotic therapy. We alternated indomethacin pretr eatment in rabbits receiving no antibiotic therapy and rabbits startin g ampicillin-sulbactam 4 hours after inoculation. RESULTS: Compared wi th saline solution inoculated control animals, those inoculated with E scherichia coli (and given no antibiotic therapy) had significant incr eases in fetal loss, fever, bleeding at 24 hours, and positive culture s (100%, 92%, 76%, 98% versus 0%, respectively, all p < 0.01). In Esch erichia coli-inoculated animals receiving no antibiotic therapy pretre atment with indomethacin significantly decreased bleeding and delivery within first 24 hours compared with those not treated with indomethac in (p < 0.05) but did not significantly improve fetal survival. Ampici llin-sulbactam treatment stated at 0, 4, 8, and 12 hours after inocula tion resulted in improved fetal survival compared with the untreated g roup (100%, 56%, 50%, 50% versus 0%, respectively, all p < 0.05). Trea tment initiated at 16 hours resulted in outcomes similar to Escherichi a coli-inoculated animals receiving no antibiotic therapy. CONCLUSION: 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, i nitiated as long as 12 hours after Escherichia coli inoculation, resul ted in significant improvement in fetal survival compared with antibio tic therapy. We believe this model mimics ascending infection in pregn ancy more closely than do previous animal models.