Treatment of ppROM With Erythromycin vs. Azithromycin Trial

In the United States, preterm premature rupture of membranes (PPROM) complicates 4% of pregnancies annually. This pregnancy complication is a major contributor to preterm births and results in neonatal morbidity and mortality. Without treatment, 70-80% of women deliver within the 1st week following membrane rupture. Multiple trials have proven that antibiotics given to this population prolong the latency from time of PPROM to delivery, hence reducing maternal and neonatal morbidities. According to the American College of Obstetrics and Gynecology, the current standard of care for PPROM subjects between the gestational age of 24 weeks and 0 days and 33 weeks and 6 days, is to administer ampicillin 2 gm IV every 6 hours for 48 hours followed by amoxicillin 250 mg orally every 8 hours for 5 days, with erythromycin 250 mg IV every 6 hours for 48 hours followed by 500 mg orally every 8 hours for 5 days. In this regimen, multiple doses of intravenous (IV) and oral (PO) doses of erythromycin are needed to achieve the desired outcome. Erythromycin can cause GI upset and some subjects do not tolerate this regimen over the course of 7 days. In addition, there is a national shortage of erythromycin, and published expert opinion proposed to use a second-generation macrolide (azithromycin) instead of erythromycin. This strategy was adopted nationwide including the maternal center at UTMB since 2014. Compared to erythromycin, advantages of azithromycin include: * It is taken once orally (due to its long intracellular half-life). * The entire regimen is much cheaper than the multiple does of erythromycin (23 doses). * It has less gastrointestinal adverse effects. As a result, azithromycin is now commonly being used as a substitute for erythromycin on many labor and delivery units around the country. Despite its common use, there exists no level 1 evidence that azithromycin is equivalent to erythromycin. Haas and colleagues published a retrospective comparison of the two regimens in 2014 and concluded that the substitution of azithromycin for erythromycin in the recommended antibiotic regimen did not impact latency or any other measured maternal or fetal outcomes. This study, however, was limited by its non-randomized retrospective nature. The investigators' objective is to compare the effectiveness of the 2 regimens in prolonging pregnancy after PPROM. This trial will be a comparative effectiveness pragmatic randomized trial performed in singleton pregnancies with the diagnosis of PPROM between 24 weeks and 0 days - 32 weeks and 6 days. It will be comparing two well-accepted standardized treatments of care in this subject population: Erythromycin (FDA Category B) versus Azithromycin (FDA Category B). The investigators' primary outcome will be the proportion of women still pregnant by day 7 after the diagnosis of PPROM is made. The investigators' working hypothesis is that there is no measurable difference in the primary outcome between the group randomized to the azithromycin regimen versus the group randomized to the erythromycin regimen. The investigators' secondary outcome will be latency defined as interval from PPROM to delivery. Data to be collected will consist of demographics, obstetrical history, relevant vital signs and laboratories. Examples of data to be collected but not limited to include: age, ethnicity/race, gravida, para, received tocolytics, received antenatal steroids, gestational age at rupture of membranes, reason for delivery, mode of delivery, gestational age at delivery, chorioamnionitis, date \& time of initiation of antibiotics, date \& time of delivery, placental abruption, hospital length of stay, number of women undelivered at day 7 of admission, NICU admission, infant intubation days, neonatal NEC and neonatal sepsis. In addition, drug adverse effects profiles between the two will be assessed in a post treatment patient survey. The latter will be assessing the severity and incidence of diarrhea and other symptoms such as nausea and vomiting and their severity. The investigators propose a total of 324 subjects will be needed to complete the study.