Shahrekord University of Medical Sciences Journal of Multidisciplinary Care 2783-3852 13 3 2025 10 19 Comparative Analysis of Maternal and Neonatal Outcomes Associated with Ampicillin–Azithromycin versus Ampicillin–Cefazolin Regimens in Cases of Preterm Premature Rupture of Membranes: A Randomized Controlled Trial 137 141 10.34172/jmdc.1394 EN Somayeh Khanjani https://orcid.org/0000-0002-2911-2001 Zynab Zeraatpishe https://orcid.org/0009-0000-6177-6556 Elahe Zarean https://orcid.org/0000-0002-0246-9529 Farinaz Farahbod https://orcid.org/0000-0002-5211-6932 Journal Article 10.34172/jmdc.1394 2025 04 18 2025 08 19 Background and aims: This study aimed to compare the efficacy of two prophylactic antibiotic regimens—ampicillin plus azithromycin versus ampicillin plus cefazolin—on maternal and neonatal outcomes in women with preterm premature rupture of membranes (PPROM). Methods: In this parallel-group randomized controlled trial, 90 pregnant women with PPROM between 26 and 37 weeks of gestation were randomly assigned to receive either ampicillin with azithromycin or ampicillin with cefazolin. Data on maternal and neonatal outcomes were collected from hospital records and analyzed using SPSS version 26. Results: The baseline characteristics, including maternal age, gestational age, and medical history, were comparable between the two groups. Maternal outcomes, such as leukocytosis, fever, incision discharge, and hematomas, did not demonstrate statistically significant differences between the regimens. Neonatal Apgar scores at 1 and 5 minutes were also similar (P>0.05). However, the duration of amniotic sac rupture was significantly shorter in the ampicillin and cefazolin group (median=12 hours, interquartile range=15) compared to the ampicillin and azithromycin group (median=18 hours, interquartile range=9; P=0.033). Conclusion: While most maternal and neonatal outcomes did not differ significantly between the two regimens, the shorter duration of amniotic sac rupture in the ampicillin and cefazolin group suggests potential advantages in reducing infection risks. Further studies are warranted to validate these findings and to optimize antibiotic regimens for the management of PPROM.