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Background: Sepsis is a leading cause of direct and indirect maternal death in both the UK and globally. All forms of operative delivery are associated with an increased risk of sepsis, and the National Institute for Health and Care Excellence's guidance recommends the use of prophylactic antibiotics at all caesarean deliveries, based on substantial randomised controlled trial evidence of clinical effectiveness. A Cochrane review, updated in 2017 (Liabsuetrakul T, Choobun T, Peeyananjarassri K, Islam QM. Antibiotic prophylaxis for operative vaginal delivery. Cochrane Database Syst Rev 2017; 8 :CD004455), identified only one small previous trial of prophylactic antibiotics following operative vaginal birth (forceps or ventouse/vacuum extraction) and, given the small study size and extreme result, suggested that further robust evidence is needed., Objectives: To investigate whether or not a single dose of prophylactic antibiotic following operative vaginal birth is clinically effective for preventing confirmed or presumed maternal infection, and to investigate the associated impact on health-care costs., Design: A multicentre, randomised, blinded, placebo-controlled trial., Setting: Twenty-seven maternity units in the UK., Participants: Women who had an operative vaginal birth at ≥ 36 weeks' gestation, who were not known to be allergic to penicillin or constituents of co-amoxiclav and who had no indication for ongoing antibiotics., Interventions: A single dose of intravenous co-amoxiclav (1 g of amoxicillin/200 mg of clavulanic acid) or placebo (sterile saline) allocated through sealed, sequentially numbered, indistinguishable packs., Main Outcome Measures: Primary outcome - confirmed or suspected infection within 6 weeks of giving birth. Secondary outcomes - severe sepsis, perineal wound infection, perineal pain, use of pain relief, hospital bed stay, hospital/general practitioner visits, need for additional perineal care, dyspareunia, ability to sit comfortably to feed the baby, maternal general health, breastfeeding, wound breakdown, occurrence of anaphylaxis and health-care costs., Results: Between March 2016 and June 2018, 3427 women were randomised: 1719 to the antibiotic arm and 1708 to the placebo arm. Seven women withdrew, leaving 1715 women in the antibiotic arm and 1705 in the placebo arm for analysis. Primary outcome data were available for 3225 out of 3420 women (94.3%). Women randomised to the antibiotic arm were significantly less likely to have confirmed or suspected infection within 6 weeks of giving birth (180/1619, 11%) than women randomised to the placebo arm (306/1606, 19%) (relative risk 0.58, 95% confidence interval 0.49 to 0.69). Three serious adverse events were reported: one in the placebo arm and two in the antibiotic arm (one was thought to be causally related to the intervention)., Limitations: The follow-up rate achieved for most secondary outcomes was 76%., Conclusions: This trial has shown clear evidence of benefit of a single intravenous dose of prophylactic co-amoxiclav after operative vaginal birth. These results may lead to reconsideration of official policy/guidance. Further analysis of the mechanism of action of this single dose of antibiotic is needed to investigate whether earlier, pre-delivery or repeated administration could be more effective. Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for pre-delivery administration., Trial Registration: Current Controlled Trials ISRCTN11166984., Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 54. See the National Institute for Health Research Journals Library website for further project information., Competing Interests: Oliver Rivero-Arias, Ursula Bowler, Edmund Juszczak, Marian Knight, Louise Linsell and Julia Sanders report receipt of funding from the National Institute for Health Research (NIHR) outside the submitted work. Edmund Juszczak reports Clinical Trials Unit infrastructure support funding received from NIHR and active membership of the Health Technology Assessment (HTA) Commissioning Board and the HTA General Board while the study was being undertaken.

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., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Sepsis is one of the most important causes of maternal death and severe morbidity worldwide. Studies conducted both in the UK and US have documented an additional risk associated with operative vaginal delivery. However, a Cochrane review, updated in 2017, identified only one small trial of prophylactic antibiotics following operative vaginal delivery, which included a total of 393 women. Given the small size of that trial, it recommended that further robust evidence is needed. Operative vaginal delivery rates vary worldwide, but typically 5-10% of women have operative vaginal births. A conservative estimated incidence of maternal infection following operative vaginal delivery is 4%, based on the one previous trial. There is, therefore, considerable scope for direct patient benefit from an effective preventive strategy., Methods/design: This protocol describes a multicentre, randomised, blinded, placebo-controlled trial aiming to recruit 3424 participants from over 20 hospital sites in the UK. Women who have undergone an operative vaginal delivery at 36 +0 weeks or greater gestation with no indication for ongoing antibiotics in the postpartum period and no contra-indications to prophylactic co-amoxiclav, will be randomised to receive a single intravenous dose of co-amoxiclav or placebo. The primary outcome will be confirmed or suspected maternal infection within 6 weeks of delivery, as defined by one of (a) a new prescription of antibiotics for presumed perineal wound-related infection, endometritis or uterine infection, urinary tract infection with systemic features or other systemic infection, (b) systemic infection confirmed with a culture or (c) endometritis as defined by the US Centers for Disease Control and Prevention. Outcome information will be collected by a single telephone interview and questionnaire, with clinical data collected from medical records or the hospital laboratory if necessary, at 6 weeks post-delivery., Discussion: This randomised trial will investigate whether a prophylactic dose of antibiotic following operative vaginal delivery can reduce the incidence of infection and sepsis. If shown to be effective, this could lead to a change in recommended practice and the prevention of infection. Conversely, if there is no significant difference between the two arms, then this could contribute to a reduction in antibiotic use and improved antimicrobial stewardship., Trial Registration: ISRCTN11166984 . Registered on 23 September 2015.