Outcomes after extended azithromycin administration in preterm premature rupture of membranes

BACKGROUND: Preterm premature rupture of membranes accounts for approximately one-quarter of all preterm deliveries and occurs in 2% to 3% of all pregnancies. With subclinical infection being a suspected cause of preterm premature rupture of membranes, the administration of prophylactic antibiotics is an accepted standard of care to extend the latency period. Historically, erythromycin was used in the antibiotic regimen recommended for women with preterm premature rupture of membranes during expectant management; however, azithromycin has recently been shown to be a suitable alternative. OBJECTIVE: This study aimed to evaluate whether extended azithromycin administration affects the latency time in preterm premature rupture of membranes. STUDY DESIGN: This was a retrospective multi-institutional cohort study in Washington, District of Columbia, of patients admitted from January 2012 to December 2019 with preterm premature rupture of membranes of singleton pregnancies between 23 0/7 and 33 6/7 weeks of gestation. Patients were excluded if they had multiple pregnancies, had an allergy to penicillin or macrolides, were in labor, had suspected placental abruptions, had overt chorioamnionitis, or had nonreassuring fetal status on presentation indicating the need for prompt delivery. Patients that received limited azithromycin administration (<2 days) and patients that received extended azithromycin administration (7 days) were compared. All patients otherwise received the institutional standard of 2 days of intravenous ampicillin followed by 5 days of oral amoxicillin. The primary outcome was length of gestational latency, defined as the time from membrane rupture to delivery. The selective secondary outcomes that were evaluated were rates of chorioamnionitis and adverse neonatal outcomes, including sepsis, respiratory distress, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal death. RESULTS: During the study period, 416 cases of preterm premature rupture of membranes were identified. Of the 287 patients who met the inclusion criteria, 165 (57.5%) received limited azithromycin administration, and 122 (42.5%) received extended azithromycin administration. Adjusted median gestational latency was significantly longer for patients who received extended azithromycin administration, extended by >3 days (2.6 days [interquartile range, 2.2–3.1] for limited azithromycin administration vs 5.8 days [interquartile range, 4.8–6.9] for extended azithromycin administration; P<.001). Neonatal secondary outcome evaluation was performed on 216 cases (76%). There was no difference in chorioamnionitis or adverse neonatal outcomes between the 2 groups. CONCLUSION: Among patients with preterm premature rupture of membranes, extended azithromycin administration was associated with increased latency, without any effect on other maternal or neonatal outcomes.