BACKGROUND: Following the destruction of pharmaceutical production facilities in Puerto Rico by Hurricane Maria in September 2017, a shortage of small-volume bags of sterile intravenous fluid for infusion led to a decreased ability to administer intravenous azithromycin and ampicillin efficiently for use in the treatment of patients with preterm premature rupture of membranes. OBJECTIVE: This study aimed to assess pregnancy latency after preterm premature rupture of membranes following treatment with oral-only antibiotics compared with treatment with intravenous antibiotics followed by oral antibiotics. STUDY DESIGN: This is a retrospective historic control study comparing women with preterm premature rupture of membranes who were initiated on a 7-day oral-only regimen of azithromycin and amoxicillin (modified regimen) during a 12-month period beginning December 2017 (during which time there was a shortage of small-volume bags of intravenous fluid) to women with preterm premature rupture of membranes who were initiated on a 2-day regimen of intravenous ampicillin and azithromycin followed by 5 days of oral amoxicillin and azithromycin (standard regimen) from December 2016 to December 2018. Women were included in the study if they were diagnosed with preterm premature rupture of membranes at <34 weeks' gestation and were started on latency antibiotics, and women were excluded from the study if they had a contraindication to expectant management, a cerclage, or suspected fetal anomalies. The primary outcome was pregnancy latency, defined as time from the first dose of antibiotics to delivery. RESULTS: The 37 women who received the modified regimen and the 79 women who received the standard regimen had similar baseline characteristics. Mean (standard deviation) gestational age at time of preterm premature rupture of membranes was similar between the modified (30.5 weeks' gestation [±3.1]) and standard regimen groups (30.2 weeks' gestation [±3.2]), and the rate of group B streptococcus rectovaginal colonization was similar for both groups (27% vs 24%; P=.95). Pregnancy latency did not differ in the modified vs standard regimen (mean difference, -0.15 days; 95% confidence interval, -4.87 to 4.58) There was no statistically significant difference in the relative risk of composite maternal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.53) or composite neonatal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.52). CONCLUSION: Although limited by small sample size, our study suggested that adoption of an oral-only antibiotic regimen for pregnancy latency following preterm premature rupture of membranes is worthy of further study.