Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, the Center for Women's Reproductive Health, and the Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, and Mission Hospital, Asheville, North Carolina; and the Departments of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas, Ochsner Health System, New Orleans, Louisiana, University of Utah and Intermountain Health Care, Salt Lake City, Utah, Columbia University, New York, New York, University of Mississippi, Jackson, Mississippi, University of Texas Health Sciences Center, Houston, Texas.
Obstet Gynecol. 2022 Jun 1;139(6):1043-1049. doi: 10.1097/AOG.0000000000004788. Epub 2022 May 2.
To estimate the association between timing of administration of adjunctive azithromycin for prophylaxis at unscheduled cesarean delivery and maternal infection and neonatal morbidity.
We conducted a secondary analysis of a randomized trial of adjunctive azithromycin prophylaxis in patients with singleton gestations who were undergoing unscheduled cesarean delivery. The primary exposure was the timing of initiation of the study drug (after skin incision or 0-30 minutes, more than 30-60 minutes, or more than 60 minutes before skin incision). The primary outcome was a composite of endometritis, wound infection, and other maternal infections occurring up to 6 weeks after cesarean delivery. Secondary outcomes included composite neonatal morbidity, neonatal intensive care unit admission for longer than 72 hours, and neonatal sepsis. The association of azithromycin with outcomes was compared within each antibiotic timing group and presented as risk ratios (RRs) with 95% CIs. A Breslow-Day homogeneity test was applied to assess differences in association by antibiotic timing.
Of 2,013 participants, antibiotics were initiated after skin incision (median 3 minutes, range 0-229 minutes) in 269 (13.4%), 0-30 minutes before skin incision in 1,378 (68.5%), more than 30-60 minutes before skin incision in 270 (13.4%), and more than 60 minutes before skin incision (median 85 minutes, range 61-218 minutes) in 96 (4.8%). The RRs (95% CIs) of the infectious composite outcome for azithromycin compared with placebo were significantly lower for groups that initiated azithromycin after skin incision or within 1 hour before skin incision (after skin incision: RR 0.31, 95% CI 0.13-0.76; 0-30 minutes before: RR 0.62, 95% CI 0.44-0.89; more than 30-60 minutes before: 0.31, 95% CI 0.13-0.66). Risks were not significantly different in patients who received azithromycin more than 60 minutes before skin incision (RR 0.59, 95% CI 0.10-3.36). Results were similar when endometritis and wound infections were analyzed separately. Neonatal outcomes were not significantly different for azithromycin compared with placebo across all timing groups.
Adjunctive azithromycin administration up to 60 minutes before or at a median of 3 minutes after skin incision was associated with reduced risks of maternal composite postoperative infection in unscheduled cesarean deliveries.
ClinicalTrials.gov, NCT01235546.
评估在择期剖宫产时辅助使用阿奇霉素进行预防的时机与产妇感染和新生儿发病率之间的关联。
我们对一项针对单胎妊娠患者的辅助使用阿奇霉素预防择期剖宫产的随机试验进行了二次分析。主要暴露因素为研究药物开始使用的时间（切皮后或 0-30 分钟、30-60 分钟、60 分钟前）。主要结局是剖宫产术后 6 周内发生子宫内膜炎、伤口感染和其他产妇感染的复合结局。次要结局包括复合新生儿发病率、新生儿重症监护病房（NICU）入住时间超过 72 小时和新生儿败血症。在每个抗生素使用时机组内比较阿奇霉素与结局的关联，并以风险比（RR）及其 95%置信区间（CI）呈现。应用 Breslow-Day 同质性检验评估抗生素使用时机对关联的影响。
在 2013 名参与者中，269 名（13.4%）在切皮后开始使用抗生素（中位时间为 3 分钟，范围 0-229 分钟），1378 名（68.5%）在切皮前 0-30 分钟开始使用抗生素，270 名（13.4%）在切皮前 30-60 分钟开始使用抗生素，96 名（4.8%）在切皮前 60 分钟以上开始使用抗生素（中位时间为 85 分钟，范围 61-218 分钟）。与安慰剂相比，阿奇霉素组的感染复合结局的 RR（95%CI）在切皮后或切皮前 1 小时内开始使用阿奇霉素的组显著较低（切皮后：RR 0.31，95%CI 0.13-0.76；0-30 分钟前：RR 0.62，95%CI 0.44-0.89；30-60 分钟前：0.31，95%CI 0.13-0.66）。在切皮前 60 分钟以上开始使用阿奇霉素的患者中，风险无显著差异（RR 0.59，95%CI 0.10-3.36）。当分别分析子宫内膜炎和伤口感染时，结果相似。在所有时间组中，与安慰剂相比，阿奇霉素组的新生儿结局无显著差异。
在择期剖宫产时，辅助使用阿奇霉素的时机在切皮前 60 分钟内或切皮后 3 分钟内中位数时，与降低择期剖宫产产妇术后复合感染的风险相关。
ClinicalTrials.gov，NCT01235546。
