Comparative Effectiveness of Azithromycin versus Erythromycin for Latency Prolongation in Preterm Prelabor Rupture of Membranes < 34 Weeks of Gestation

Objective: Preterm prelabor rupture of membranes (PPROM) is a major contributor to preterm birth and neonatal morbidity. Although azithromycin is increasingly used as an alternative to erythromycin for latency antibiotic therapy, comparative data remain limited. This study evaluated whether azithromycin is associated with latency duration and maternal–neonatal outcomes comparable to those of erythromycin in pregnancies complicated by PPROM before 34 weeks of gestation. Methods: A retrospective cohort study was conducted at a tertiary referral hospital by reviewing medical records from January 2011 through December 2024. Pregnant women with PPROM at 24 to < 34 weeks of gestation who completed latency antibiotic regimens were included and categorized into azithromycin or erythromycin groups. The primary outcome was latency period (time from membrane rupture to delivery). Secondary outcomes included maternal infectious complications and neonatal morbidity and mortality. Multivariable logistic regression was performed to adjust for baseline differences between groups. Results: A total of 720 participants were included (56 azithromycin; 664 erythromycin). Baseline characteristics were generally comparable, although maternal age, monthly income, and previous PPROM differed between groups. Median latency duration did not differ significantly between azithromycin and erythromycin overall (3.70 vs 3.23 days; P = 0.287) or across gestational-age subgroups. After adjustment for baseline differences, the likelihood of achieving latency ≥ 3 days was similar between groups. Maternal outcomes were largely comparable, although postpartum endometritis occurred more frequently in the azithromycin group with small event numbers. Neonatal outcomes were generally similar; NICU admission was lower, whereas intraventricular hemorrhage was more frequent in the azithromycin group, both based on small numbers. Conclusion: Azithromycin was associated with latency duration and maternal–neonatal outcomes comparable to those of erythromycin and represents a practical alternative regimen for PPROM management. Prospective studies are warranted to confirm these findings. Plain Language Summary: When a pregnant woman experiences preterm prelabor rupture of membranes (PPROM), her water breaks too early before labor begins. This can increase the risk of infection and early birth. To help reduce these risks and safely prolong pregnancy, doctors routinely give antibiotics. Erythromycin has traditionally been used for this purpose. However, azithromycin is increasingly used because it is easier to take, better tolerated, and more widely available in some settings. Despite this, there is still limited evidence directly comparing these two antibiotics. In this study, we reviewed the medical records of 720 pregnant women with PPROM before 34 weeks of pregnancy who received either azithromycin or erythromycin. We compared how long pregnancy continued after treatment and examined health outcomes for both the women and their babies. We found that pregnancy was prolonged for a similar length of time in both groups. Most maternal and neonatal outcomes were also similar between the two treatments. Some differences were observed in rare complications, but these findings should be interpreted cautiously because of the small number of cases. Overall, our results suggest that azithromycin works as well as erythromycin for managing PPROM and may be a practical alternative, especially where erythromycin is less available or more difficult to use. Further studies are needed to confirm these findings and assess long-term outcomes for children. Keywords: azithromycin, erythromycin, latency period, PPROM, preterm prelabor rupture of membranes