Intravenous co-amoxiclav to prevent infection after operative vaginal delivery: the ANODE RCT

Abstract

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.

Obstetric anal sphincter injury in the second birth after perineal wound complication in the first birth: A nationwide register cohort study

“…26,27 A randomised controlled trial published in 2019 (the ANODE trial) showed that a single dose of antibiotics after operative vaginal delivery reduced the risk of developing maternal infection from 19% to 11% (relative risk 0.58, 95% 0.49-0.69). 15 In the ANODE trial, 89% of women had an episiotomy, compared with a rate of 30.3% in our cohort. In a secondary analysis of the ANODE trial, Humphreys et al found that episiotomy, compared with no episiotomy, increased the odds of wound infection to almost threefold, but that antibiotics reduced the risk of infection irrespective of the type and degree of perineal injury.…”

“…4,14 A large randomised controlled trial has shown that prophylactic antibiotics should be considered in all operative vaginal deliveries, as it reduces the risk of postpartum infection. 14,15 The prevalence of recurrent OASI is reported as 1.0%-10.7%. 16 Recurrent OASI has an important long-term negative impact on quality of life and pelvic floor function.…”

Combination therapy: synergism among three plant extracts against selected pathogens

“…It is on this score that the World Health Organization (WHO) has promoted the use of artemisinin combination therapies (ACTs) in the treatment of Plasmodium falciparum malaria to enhance efficacy and reduce resistance. Another renowned antimicrobial agent exhibiting a significant synergistic effect in combination is Co-amoxiclav [ 20 ].…”

Penyembuhan Luka Perineum Pada Ibu Nifas Dengan Menggunakan Ekstrak Sidaguri (Sida Rhombifolia)

“…Antibotik profilasis meningkatkan nyeri perineum dan konsekuensi kesehatan terkait dengan nyeri yang di rasakan ibu nifas. 11 Pemberian antibiotik pada ibu nifas di awal tidak memberikan pengaruh terhadap kejadi infeksi perinem, begitupun pemberian antibiotic di awal persalinan masih memerlukan penelituan lanjutan sehingga tidak perlu diberiakn antibiotic di awal. Sehingga pemberian antibiotik tidak menjadi anjuran dalam pemberian pelayanan di awal untuk pencegahan infeksi karena insidensi resitesi.…”

“…Sehingga pemberian antibiotik tidak menjadi anjuran dalam pemberian pelayanan di awal untuk pencegahan infeksi karena insidensi resitesi. 11 Pemberian natibiotik pada ibu dengan luka perineum tidak memberiak efek signifikan yang dimana antara yang diberikan dan tidak diberikan memiliki penyembuhan luka perineum yang sama. 12 Sida rhombifolia memiliki Antibakteri yang signifikan terhadap dan mengandung antioksidan, genotoksik IC50 974,5 G ML-1 0,97 dan 548,4g ML-1 yang memiliki efek yang sama dengan obat yang terstandar yang ada.…”