Azithromycin versus erythromycin for the management of preterm premature rupture of membranes

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Preterm premature rupture of membranes (PPROM) complicates 2-3% of pregnancies. Many institutions have advocated for the use of azithromycin instead of erythromycin. This is secondary to national shortages of erythromycin, ease of administration, better side effect profile and decreased cost of azithromycin as compared to erythromycin.


To evaluate if there are differences in the latency from PPROM to delivery in patients treated with different dosing regimens of azithromycin vs. erythromycin.


This is a multicenter, retrospective cohort of women with singleton pregnancies with confirmed rupture of membranes between 230 to 336 weeks from January 2010 to June 2015. Patients were excluded if there was a contraindication to expectant management of PPROM. Patients received one of four antibiotic regimens: 1) azithromycin 1000 mg PO once (azithromycin 1 day group), 2) azithromycin 500 mg PO once, followed by azithromycin 250 mg PO daily for 4 days (azithromycin 5 day group), 3) azithromycin 500 mg IV for 2 days, followed by azithromycin 500 mg PO daily for 5 days (azithromycin 7 day group), or 4) erythromycin IV for 2 days followed by erythromycin PO for 5 days (erythromycin group). The choice of macrolide was based on institutional policy and/or availability of antibiotics at the time of admission. In addition, all patients received ampicillin IV for 2 days followed by amoxicillin PO for 5 days. Primary outcome was latency from diagnosis of rupture of membranes to delivery. Secondary outcomes included clinical and histopathologic chorioamnionitis and neonatal outcomes.


453 patients were identified who met inclusion criteria. 78 patients received azithromycin for 1 day, 191 patients received azithromycin for 5 days, 52 patients received azithromycin for 7 days, and 132 patients received erythromycin. Women who received the 5 day regimen were younger and less likely to be non-African American, have hypertension, sexually transmitted infection or substance abuse. There was no statistical difference in median latency time of azithromycin 1 day (4.9 days, 95% CI 3.3-6.4), azithromycin 5 day (5.0, 95% CI 3.9-6.1), or azithromycin 7 days (4.9 days. 95% CI 2.8-7.0), when compared to erythromycin (5.1 days, 95% CI 3.9-6.4) after adjusting for demographic variables (p=0.99). Clinical chorioamnionitis was not different between groups in the adjusted model. Respiratory distress syndrome (RDS) was increased in the azithromycin 5 day group vs azithromycin 1 day vs, erythromycin (44% vs. 29% and 29%, p=.005, respectively).


There was no difference in latency to delivery, incidence of chorioamnionitis, or neonatal outcomes when comparing different dosing regimens of the azithromycin with erythromycin, with exception of RDS being more common in the 5 day azithromycin group. Azithromycin could be considered as an alternative to erythromycin in the expectant management of PPROM if erythromycin is unavailable or contraindicated. There appears to be no additional benefit to an extended course of azithromycin beyond the single day dosing, but final recommendations on dosing strategies should rely on clinical trials.