A novel extended prophylactic antibiotic regimen in preterm pre-labor rupture of membranes: A randomized trial

Objectives: Prophylactic antibiotic use in preterm pre-labor rupture of membranes (PPROM) is associated with a significant reduction in intra-amniotic infection and improved neonatal outcome. However, data is insufficient to determine the optimal antibiotic regimen. Considering the rise in Escherichia coli and Klebsiella pneumonia early-onset sepsis rate and the emergence of ampicillin resistance, our aim is to compare the efficiency of two antibiotic regimens in prolonging pregnancy and reducing infectious morbidity. Design: This multicenter randomized unblinded controlled prospective trial compared two antibiotic prophylactic protocols in PPROM: ampicillin + roxithromycin vs. cefuroxime + roxithromycin in 84 women with PPROM, from 12/2015-12/2019. Results: The median latency period was significantly longer (p = 0.039) in the cefuroxime + roxithromycin group (4.63 [0.59–50.18] days) than in the ampicillin + roxithromycin group (2.3 [0.15–58.3] days). Neonatal admission to neonatal intensive care unit rate, hospitalization length, neonatal respiratory distress syndrome, neonatal fever, and need for respiratory support or mechanical ventilation, were similar between the groups. K. pneumonia cultures were significantly more frequent in the ampicillin + roxithromycin group. None of the cultures were group B Streptococcus positive. Conclusions: To prolong latency period and reduce gram-negative early-onset sepsis, cefuroxime + roxithromycin is recommended as the first-line protocol in PPROM. Clinical trial registration: ClinicalTrials.gov Identifier: NCT02819570.