A randomized clinical trial of antibiotic treatment duration in preterm premature rupture of membranes: 7 days versus until delivery.

Abstract

Antibiotic treatment in preterm premature rupture of membranes (PPROM) can prolong the interval from membrane rupture to delivery and improve neonatal outcomes; however the duration of antibiotic treatment for PPROM has rarely been compared in prospective studies. To investigate the optimal duration of antibiotic treatment for PPROM, we performed a randomized controlled trial comparing neonatal morbidity and infantile neurological outcomes between two groups of PPROM patients who received antibiotic treatment for 7 days or until delivery. This prospective randomized study included patients who were diagnosed with PPROM between 22+0 weeks and 33+6 weeks of gestation. The enrolled patients were randomly assigned to receive intravenous cefazolin (1 g dose every 12 hours) and oral clarithromycin (500 mg dose every 12 hours) for 7 days or until delivery. The study protocol was registered at clinicaltrials.gov (NCT01503606). The primary outcome was neonatal composite morbidity, and the secondary outcome was neurological outcomes at 12 months of corrected age. We enrolled 150 patients and allocated 74 and 76 of them to the 7-day and until-delivery groups, respectively. Analysis was done by per protocol. After excluding cases lost to follow-up or with protocol violations, 63 (7-day regimen) and 61 (until-delivery regimen) PPROM patients and their babies were compared. There was no significant difference in pregnancy outcomes, including gestational age at delivery and interval from rupture of membranes (ROM) to delivery, between the two groups. Among the neonatal outcomes, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and proven neonatal sepsis did not differ between the groups. However, the rate of respiratory distress syndrome (RDS) (32.8% vs. 50.8%, P=.039) and composite neonatal morbidities (34.4% vs. 53.9%, P=.026) were lower in the until-delivery group compared to the 7-day group. This difference remained statistically significant after a multivariable analysis adjusting for maternal age, twin pregnancy, use of antenatal corticosteroids, the ROM to delivery interval, and gestational age at delivery. Infantile neurological outcomes were evaluated in 70% of the enrolled patients and did not differ between the groups. Overall, until-delivery regimen of cefazolin and clarithromycin in PPROM showed lower incidence of composite neonatal morbidities, and of RDS compared to the 7-day regimen and both regimens showed otherwise similar other individual neonatal morbidities and infantile neurological outcomes.