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 inoculation of Escherichia coli we investigated the effects of administration of delayed antibiotics and indomethacin on outcomes.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver 80262.
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L
Heddleston
R S
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McDuffie
R S
RS
Gibbs
D000667:Ampicillin / Q000627:therapeutic use*; D000818:Animals; D002821:Chorioamnionitis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D004927:Escherichia coli Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D007213:Indomethacin / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000401:mortality; D011292:Premedication; D011817:Rabbits; D013407:Sulbactam / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D002577:Uterine Cervical Diseases / Q000150:complications / Q000188:drug therapy / Q000401:mortality
C035444:sultamicillin; D000667:Ampicillin; D013407:Sulbactam; D007213:Indomethacin