牛津大学Marian Knight教授研究组近日针对阴道分娩是否需要预防性应用抗菌药物，开展了中心随机对照试验。研究成果于2019年6月发表在国际学术期刊《柳叶刀》上。

该课题组的目的是调查抗生素预防是否可以预防产妇阴道分娩后感染。 在一项在英国27个产科单位进行的盲法随机对照试验中，年龄≥16岁的妇女在妊娠36周或更晚的阴道手术分娩后被分配接受单剂量的阿莫西林和克拉维酸或安慰剂(生理盐水)静脉注射。主要判定是在分娩后6周内确诊或疑似母体感染，具体指征采用新的抗生素处方确定，培养时确诊全身感染或子宫内膜炎。

研究组做了一个意向治疗分析。该试验在ISRCTN登记，编号为11166984，并关闭权责发生制。在2016年3月13日至2018年6月13日期间，3427名女性被随机分配到治疗组：1719名接受阿莫西林和克拉维酸治疗，1708名接受安慰剂治疗。七名妇女退出，1715名阿莫西林和克拉维酸组和1705名安慰剂组。195名(6%)妇女的主要结果数据缺失。使用阿莫西林和克拉维酸的妇女确诊或疑似感染的人数(1619例中180例[11%])明显少于使用安慰剂的妇女(1606例中306例[19%]);风险比0·58,95% CI 0·49-0·69;术;0·0001)。安慰剂组的一名女性报告出现皮疹，服用阿莫西林和克拉维酸的两名女性报告出现其他过敏反应，其中一名报告出现严重不良反应。另有两例严重不良事件被报道，但均未被认为与治疗有因果关系。这项试验表明，在阴道手术分娩后使用单剂量预防性抗生素的益处，应改变世卫组织和其他国家组织的指导意见。

据了解，产妇感染的危险因素得到了明确的认识，包括剖腹产和阴道手术分娩。抗生素预防在剖宫产是广泛推荐的，因为有明确的系统回顾证据表明，它能够有效降低产妇感染的发生率。目前世卫组织指南不建议对阴道分娩的妇女进行常规抗生素预防，因为缺乏有效证据。 

附：英文原文

Title: Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial

Author:Marian Knight,Virginia Chiocchia, Christopher Partlett,Oliver Rivero-Arias,Xinyang Hua, Kim Hinshaw,Derek Tuffnell, Louise Linsell, Edmund Juszczak

Issue&Volume: Volume 393,Number 10189,2019

Abstract:

Background

Risk factors for maternal infection are clearly recognised, including caesarean section and operative vaginal birth. Antibiotic prophylaxis at caesarean section is widely recommended because there is clear systematic review evidence that it reduces incidence of maternal infection. Current WHO guidelines do not recommend routine antibiotic prophylaxis for women undergoing operative vaginal birth because of insufficient evidence of effectiveness. We aimed to investigate whether antibiotic prophylaxis prevented maternal infection after operative vaginal birth.

Methods

In a blinded, randomised controlled trial done at 27 UK obstetric units, women (aged ≥16 years) were allocated to receive a single dose of intravenous amoxicillin and clavulanic acid or placebo (saline) following operative vaginal birth at 36 weeks gestation or later. The primary outcome was confirmed or suspected maternal infection within 6 weeks of delivery defined by a new prescription of antibiotics for specific indications, confirmed systemic infection on culture, or endometritis. We did an intention-to-treat analysis. This trial is registered with ISRCTN, number 11166984, and is closed to accrual.

Findings

Between March 13, 2016, and June 13, 2018, 3427 women were randomly assigned to treatment: 1719 to amoxicillin and clavulanic acid, and 1708 to placebo. Seven women withdrew, leaving 1715 in the amoxicillin and clavulanic acid group and 1705 in the placebo groups. Primary outcome data were missing for 195 (6%) women. Significantly fewer women allocated to amoxicillin and clavulanic acid had a confirmed or suspected infection (180 [11%] of 1619) than women allocated to placebo (306 [19%] of 1606; risk ratio 0·58, 95% CI 0·49–0·69; p<0·0001). One woman in the placebo group reported a skin rash and two women in the amoxicillin and clavulanic acid reported other allergic reactions, one of which was reported as a serious adverse event. Two other serious adverse events were reported, neither was considered causally related to the treatment.

Interpretation

This trial shows benefit of a single dose of prophylactic antibiotic after operative vaginal birth and guidance from WHO and other national organisations should be changed to reflect this.

DOI: https://doi.org/10.1016/S0140-6736(19)30773-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30773-1/fulltext#