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

Lancet. 2019 Jun 15;393(10189):2395-2403. doi: 10.1016/S0140-6736(19)30773-1. Epub 2019 May 13.

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.

Funding: NIHR Health Technology Assessment programme.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amoxicillin-Potassium Clavulanate Combination / administration & dosage*
  • Anti-Bacterial Agents / administration & dosage*
  • Antibiotic Prophylaxis*
  • Delivery, Obstetric / adverse effects*
  • Female
  • Humans
  • Intention to Treat Analysis
  • Middle Aged
  • Pregnancy
  • Puerperal Infection / prevention & control*
  • Surgical Wound Infection / prevention & control*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Amoxicillin-Potassium Clavulanate Combination