Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Massachusetts-Baystate, Springfield, MA.
Am J Obstet Gynecol. 2019 Aug;221(2):144.e1-144.e8. doi: 10.1016/j.ajog.2019.03.009. Epub 2019 Mar 20.
Preterm premature rupture of membranes 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 with erythromycin.
The objective of the study was to evaluate whether there are differences in the latency from preterm premature rupture of membranes 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 23 and 33 weeks from January 2010 to June 2015. Patients were excluded if there was a contraindication to expectant management of preterm premature rupture of membranes. Patients received 1 of 4 antibiotic regimens: (1) azithromycin 1000 mg per os once (azithromycin 1 day group); (2) azithromycin 500 mg per os once, followed by azithromycin 250 mg per os daily for 4 days (azithromycin 5 day group); (3) azithromycin 500 mg intravenously for 2 days, followed by azithromycin 500 mg per os daily for 5 days (azithromycin 7 day group); or (4) erythromycin intravenously for 2 days followed by erythromycin per os 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 intravenously for 2 days followed by amoxicillin per os for 5 days. Primary outcome was latency from diagnosis of rupture of membranes to delivery. Secondary outcomes included clinical and histopathological chorioamnionitis and neonatal outcomes.
Four hundred fifty-three patients who met inclusion criteria were identified. Seventy-eight 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, have sexually transmitted infection, or experienced substance abuse. There was no statistical difference in median latency time of azithromycin 1 day (4.9 days, 95% confidence interval, 3.3-6.4), azithromycin 5 days (5.0, 95% confidence interval, 3.9-6.1), or azithromycin 7 days (4.9 days, 95% confidence interval, 2.8-7.0) when compared with erythromycin (5.1 days, 95% confidence interval, 3.9-6.4) after adjusting for demographic variables (P = .99). Clinical chorioamnionitis was not different between groups in the adjusted model. Respiratory distress syndrome 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 the exception of respiratory distress syndrome being more common in the 5 day azithromycin group. Azithromycin could be considered as an alternative to erythromycin in the expectant management of preterm premature rupture of membranes 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.
胎膜早破在 2-3%的妊娠中会变得复杂。许多机构主张使用阿奇霉素代替红霉素。这是由于红霉素短缺、给药方便、副作用少、阿奇霉素的成本比红霉素低。
本研究的目的是评估与接受红霉素相比，接受不同剂量阿奇霉素治疗的患者从胎膜早破到分娩的潜伏期是否存在差异。
这是一项多中心、回顾性队列研究，纳入了 2010 年 1 月至 2015 年 6 月期间确诊为 23-33 周胎膜早破的单胎妊娠妇女。如果存在期待性治疗胎膜早破的禁忌证，则排除患者。患者接受以下 4 种抗生素方案之一：（1）阿奇霉素 1000mg 口服一次（阿奇霉素 1 天组）；（2）阿奇霉素 500mg 口服一次，然后阿奇霉素 250mg 口服，每日 4 天（阿奇霉素 5 天组）；（3）阿奇霉素 500mg 静脉注射 2 天，然后阿奇霉素 500mg 口服，每日 5 天（阿奇霉素 7 天组）；或（4）红霉素静脉注射 2 天，然后红霉素口服 5 天（红霉素组）。大环内酯类药物的选择基于机构政策和/或入院时抗生素的可用性。此外，所有患者均接受氨苄西林静脉注射 2 天，然后阿莫西林口服 5 天。主要结局是从胎膜早破诊断到分娩的潜伏期。次要结局包括临床和组织病理学绒毛膜羊膜炎和新生儿结局。
确定了符合纳入标准的 453 名患者。78 名患者接受阿奇霉素治疗 1 天，191 名患者接受阿奇霉素治疗 5 天，52 名患者接受阿奇霉素治疗 7 天，132 名患者接受红霉素治疗。接受 5 天方案的患者年龄较小，且不太可能是非非洲裔美国人、患有高血压、患有性传播感染或滥用药物。调整人口统计学变量后，与红霉素相比，阿奇霉素 1 天（4.9 天，95%置信区间 3.3-6.4）、阿奇霉素 5 天（5.0 天，95%置信区间 3.9-6.1）或阿奇霉素 7 天（4.9 天，95%置信区间 2.8-7.0）的中位潜伏期时间没有统计学差异（P=0.99）。调整模型中各组间临床绒毛膜羊膜炎无差异。与阿奇霉素 1 天组和红霉素组相比，阿奇霉素 5 天组的呼吸窘迫综合征发生率更高（44%比 29%和 29%，P=0.005）。
与红霉素相比，不同剂量的阿奇霉素治疗胎膜早破的潜伏期、绒毛膜羊膜炎发生率或新生儿结局无差异，但阿奇霉素 5 天组的呼吸窘迫综合征更常见。如果红霉素不可用或禁忌，阿奇霉素可作为红霉素期待性治疗胎膜早破的替代药物。阿奇霉素单剂量与多剂量治疗相比，没有额外的益处，但最终的剂量策略建议应依赖临床试验。
