Prophylactic antibiotics could reduce infection risk after operative vaginal delivery
Women who receive a single dose of amoxicillin and clavulanic acid within 6 hours of operative vaginal delivery could significantly reduce their postpartum infection risk, according to the UK-based ANODE* trial.
“Almost one in five women experience an infective complication and our results show that this can be reduced by almost half with routine use of antibiotic prophylaxis at operative vaginal delivery. This equates to prevention of over 7,000 infections annually in the UK,” said lead investigator Professor Marian Knight from the University of Oxford, Oxford, UK.
“These findings highlight the urgent need to change current [World Health Organization] antibiotic guidelines and other guidance from organizations in the UK, North America, and Australasia, that do not recommend routine antibiotic prophylaxis for assisted childbirth,” she added.
This multicentre (27 obstetric units in the UK) trial involved 3,427 women (aged ≥16 years) at ≥36 weeks gestation who were randomized to receive a single intravenous dose of amoxicillin (1 g) plus clavulanic acid (200 mg; n=1,719) or placebo (n=1,708) within 6 hours following a vaginal delivery requiring vacuum or forceps extraction (35 and 65 percent, respectively). Seventy-seven percent of women were primiparous, 49 percent had induction of labour, and 89 percent had undergone episiotomy. Women with a clinical indication for post-delivery antibiotic therapy were excluded.
Fifteen percent of women experienced infection, as determined by a new antibiotic prescription for perineal wound-related infection, endometritis or uterine infection, urinary tract infection with systemic involvement, or other systemic infection, or culture-diagnosed infection.
In the 6 weeks following delivery, infections occurred less frequently among women assigned to amoxicillin plus clavulanic acid than those assigned to placebo (11 percent vs 19 percent, risk ratio [RR], 0.58, 95 percent confidence interval [CI], 0.49–0.69; p<0.0001). [Lancet 2019;393:2395-2403]
The infection incidence remained lower in women assigned amoxicillin plus clavulanic acid than placebo when the analysis was limited to culture-confirmed systemic infection (0.6 percent vs 1.5 percent, RR, 0.44, 95 percent CI, 0.22–0.89; p=0.018).
The incidence of superficial or deep incisional infections were also halved in the amoxicillin plus clavulanic acid compared with the placebo group (4 percent vs 8 percent, RR, 0.53 [superficial] and 2 percent vs 5 percent, RR, 0.46 [deep]; p<0.0001 for both).
Secondary outcomes such as perineal pain (RR, 0.84; p<0.0001), wound breakdown (RR, 0.52; p<0.0001), and use of pain relief for perineal pain (RR, 0.72; p=0.0073) within 6 weeks of delivery were also less common among women assigned amoxicillin plus clavulanic acid than placebo. Systemic sepsis occurred at a similar rate between groups (p=0.307).
Three adverse events (AEs) occurred within 6 hours after antibiotic or placebo administration, one in the placebo group (skin rash) and two in the amoxicillin plus clavulanic acid group (other allergic reactions, one deemed a serious AE).
“We found that for each additional 100 doses of antibiotic used in prophylaxis, 168 treatment doses will be saved, representing a 17 percent overall reduction in antibiotic use with a policy of universal prophylaxis,” Knight added.
Future research should investigate the optimal time of antibiotic administration and the necessity of multiple doses, as well as the efficacy of oral antibiotics, noted Knight and co-authors.
In an accompanying commentary, Professor Vincenzo Berghella from Thomas Jefferson University in Philadelphia, Pennsylvania, US, and Dr Federica Bellussi from the University of Bologna in Bologna, Italy, acknowledged these potentially “practice changing” results. [Lancet 2019;393:2361-2362] Nonetheless, they underscored the importance of research into the prevention of perineal trauma, which could subsequently reduce the risk of infection.