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.

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Maternal carriage and vertical transmission of extended-spectrum, beta-lactamase-producing Enterobacteriaceae (ESBL-E), such as Escherichia coli, hamper the treatment of infections, resulting in high morbidity. E. coli is the most frequent cause of early-onset neonatal sepsis (EOS) in preterm infants, where ESBL-E are more frequently isolated. In this prospective, case-controlled study, maternal rectovaginal ESBL-E colonization and vertical transmission to preterm infants were assessed in 160 women with preterm premature rupture of membranes (PPROM; 57.4%) or preterm labor (42.6%); additional cultures were obtained from the placenta, amnion, and umbilical cord during preterm labor. Maternal and neonatal ESBL-E-carriage rates were 17.5% and 12.9%, respectively, and the vertical-transmission rate was 50%. Maternal ESBL-E colonization among women with PPROM was 21.3%, and in women with premature labor it was 12.6%. No correlation was observed between maternal ESBL-E-colonization and previous hospitalization or antibiotic administration during pregnancy. However, a correlation was found between placental inflammation and maternal ESBL-E colonization (p = 0.007). ESBL-E-colonized infants were delivered at an earlier gestational age and were more likely to have complications. Thus, the high ESBL-E carriage rate in women with threatened preterm labor, without obvious risk factors for carriage, and a high vertical transmission rate, combined with a correlation between placental inflammation and ESBL-E carriage, support maternal–neonatal ESBL-E-colonization surveillance and active measures to prevent ESBL-E-related EOS.