Antibiotic Regimens for the Management of Preterm Prelabour Rupture of Membranes: A Multicenter Retrospective Cohort Study

Abstract

Objective: Evolving bacterial ecology and resistance warrant re-evaluation of traditional antibiotic regimens for prelabour premature rupture of membranes (PPROM). This study aimed to compare delivery within 7 days of PPROM and overall latency according to different antibiotic regimens. Secondary objectives were to compare adverse maternal and neonatal outcomes.

Methods: This multicenter retrospective study utilized data from 5 Canadian hospitals from 2016 to 2022. Singleton pregnancies with PPROM at 18-34 weeks gestation were included. Cases were divided into 4 groups based on antibiotic regimen administered, and outcomes were compared using logistic and linear regression analyses, controlling for gestational age at PPROM.

Results: Of 669 PPROM cases, 50% received ampicillin/amoxicillin and macrolide, and the remainder received macrolide only (30%), macrolide and other (3%), and non-macrolide (17%) regimens. "Macrolide-only" was associated with a significantly shorter latency compared to "ampicillin/amoxicillin with macrolide" (adjusted OR for latency ≤7 days 1.9; 95% CI 1.3-2.8; and adjusted relative mean overall latency -6.7 days, 95% CI -9.3 to -4.1). Compared to other regimens, "macrolide-only" was associated with higher rates of maternal clinical and histological chorioamnionitis (37% vs. 14%-25%, P = 0.001, and 74% vs. 52%-61%, P < 0.001, respectively) and neonatal intraventricular hemorrhage (23% vs. 11%-13%, P = 0.009). Among cases of neonatal bacteremia, ampicillin resistance was frequent (11/19; 58%).

Conclusions: Macrolide alone is inferior to ampicillin/amoxicillin with a macrolide in prolonging pregnancy and preventing adverse outcomes; therefore, its use should be strongly reconsidered in women with penicillin allergy. Broader-spectrum regimens warrant further clinical investigation.

Keywords: ampicillin resistance; antibiotics; obstetric labour; penicillins; perinatology; premature; premature birth; preterm prelabour rupture of membranes; preterm premature.