Dataset Information

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

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.

SUBMITTER: Knight M

PROVIDER: S-EPMC6584562 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundSepsis 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/designThis 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.DiscussionThis 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 registrationISRCTN11166984 . Registered on 23 September 2015.

Project description:BACKGROUND:At least half of all adult women will experience infective cystitis (urinary tract infection: UTI) at least once in their life and many suffer from repeated episodes. Recurrent urinary tract infection (rUTI) in adult women is usually treated with long-term, low-dose antibiotics and current national and international guidelines recommend this as the 'gold standard' preventative treatment. Although they are reasonably effective, long-term antibiotics can result in bacteria becoming resistant not only to the prescribed antibiotic but to other antimicrobial agents. The problem of antimicrobial resistance is recognised as a global threat and the recent drive for antibiotic stewardship has emphasised the need for careful consideration prior to prescribing antibiotics. This has led clinicians and patients alike to explore potential non-antibiotic options for recurrent UTI prevention. DESIGN /METHODS:This is a multicentre, pragmatic, patient-randomised, non-inferiority trial comparing a non-antibiotic preventative treatment for rUTI in women, methenamine hippurate, against the current standard of daily low-dose antibiotics. Women who require preventative treatment for rUTI are the target population. This group is comprised of those with a diagnosis of rUTI, defined as three episodes in 1 year or two episodes in 6 months, and those with a single severe infection requiring hospitalisation. Participants will be recruited from secondary care urology / urogynaecology departments in the UK following referral with rUTI. Participants will be followed up during a 12-month period of treatment and in the subsequent 6 months following completion of the prophylactic medication. Outcomes will be assessed from patient recorded symptoms, quality of life questionnaires and microbiological examination of urine and perineal swabs. The primary outcome is the incidence of symptomatic antibiotic-treated UTI self-reported by participants during the 12-month period of preventative treatment. Health economic outcomes will also be assessed to define the cost-effectiveness of both treatments. A qualitative study will be conducted in the first 8 months of the trial to explore with participants/non-participants' and recruiting clinicians' views on trial processes and identify potential barriers to recruitment, reasons for participating and non-participation and for dropping out of the study. DISCUSSION:The study was commissioned and funded by the National Institute for Health Research (NIHR) and approved under the Medicines and Healthcare products Regulatory Agency (MHRA) notification scheme as a 'Type A' study. TRIAL REGISTRATION:International Standard Randomised Controlled Trial Number (ISRCTN), registry number: ISRCTN70219762 . Registered on 31 May 2016.

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.