Dataset Information

Prophylactic antibiotics for the prevention of infection following operative vaginal delivery (ANODE): study protocol for a randomised controlled trial.

ABSTRACT:

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.

SUBMITTER: Knight M

PROVIDER: S-EPMC6056933 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRisk 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.MethodsIn 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.FindingsBetween 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.InterpretationThis 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.FundingNIHR Health Technology Assessment programme.

Project description:OBJECTIVE:To examine the rate of surgical site infection according to the choice of antibiotics in women undergoing cesarean delivery. METHODS:We conducted a retrospective cohort study of women undergoing cesarean delivery (labored, unlabored, and scheduled) from 2012 to 2017. Women with chorioamnionitis and those who did not receive any antibiotics were excluded. Our primary outcome was defined a priori as a composite of cellulitis, endometritis, deep wound infection, abdominopelvic abscess, and sepsis. Outcomes were examined according to the choice of antibiotics: cefazolin, a standard alternative (both clindamycin and gentamicin), and inappropriate alternatives (such as clindamycin only). A multivariable logistic regression model was used to calculate the propensity score for each observation, which was the probability of receiving a particular antibiotic regimen. The propensity score-adjusted logistic regression models were conducted to calculate adjusted odds ratios (ORs) and 95% CIs. Firth's penalized likelihood approach was applied to address issues of rare events. RESULTS:Among 6,584 selected women, 6,163 (93.6%), 274 (4.2%), and 147 (2.2%) received cefazolin, a standard alternative, and inappropriate alternatives, respectively. Use of standard alternative antibiotics compared with cefazolin was not associated with increased odds of the primary outcome (crude OR 1.50 [0.92-2.46]; adjusted OR 1.63 [0.97-2.60]) but was associated with increased odds of cellulitis (crude OR 2.07 [1.16-3.70]; adjusted OR 1.93 [1.03-3.31]). Use of inappropriate alternative antibiotics compared with cefazolin was associated with increased odds of the primary outcome (crude OR 4.37 [2.80-6.83]; adjusted OR 4.13 [2.59-6.36]) as well as some components of the composite outcome such as endometritis before discharge (crude OR 6.85 [3.94-11.90]; adjusted OR 6.68 [3.69-11.44]) and cellulitis (crude OR 3.36 [1.78-6.34]; adjusted OR 3.23 [1.63-5.81]). CONCLUSION:Both standard alternative and inappropriate alternatives were associated with increased odds of surgical site infections compared with cefazolin.