ANODE

ANODE: prophylactic ANtibiotics for the prevention of infection following Operative DElivery

Trial started: 2015  Trial ended: 2018 

Summary

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.

Methods

A multicentre, randomised, blinded, placebo-controlled trial, carried out in twenty-seven maternity units in the UK. Women were allocated to receive a single dose of intravenous co-amoxiclav (1?g of amoxicillin/200?mg of clavulanic acid) or placebo (sterile saline) following operative vaginal birth at ?36 weeks’ gestation or later.

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).

Conclusion

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.

Adapted from: Knight M, Chiocchia V, Partlett C, et al. Intravenous co-amoxiclav to prevent infection after operative vaginal delivery: the ANODE RCT. Health Technology Assessment. 2019;23(54). https://doi.org/10.3310/hta23540. © Queen's Printer and Controller of HMSO 2019. Adapted for presentation on this website.