By Richard R. Watkins, MD, MS, FACP, FIDSA

Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH

Dr. Watkins reports no financial relationships relevant to this field of study.

SYNOPSIS: In a multicenter, randomized clinical trial, researchers found that a single dose of intravenous amoxicillin/clavulanic acid significantly reduced the risk of infection following operative vaginal birth (forceps or vacuum extraction) compared to placebo (180 of 1,619 [11%] vs. 306 of 1,606 [19%], respectively; P < 0.0001).

SOURCE: Knight M, Chiocchia V, Partlett C, et al. Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): A multicentre randomised controlled trial. Lancet 2019;393:2395-2403.

Approximately one-third of births in the United States occur by cesarean delivery, a proportion that is widely criticized as too great. One potential way to reduce the number of cesarean deliveries is through the use of forceps or vacuum extraction, otherwise known as operative vaginal birth (OVB). However, it is estimated that 16% of women develop an infection following OVB. Despite this risk, routine antibiotic prophylaxis is not recommended by most experts, including the World Health Organization. Therefore, Knight et al investigated whether prophylactic antibiotics would lead to fewer infections up to six weeks following OVB.

The study was a randomized, placebo-controlled trial conducted at 27 centers in the United Kingdom. Women who had undergone OVB at 36 weeks or greater gestation were randomly assigned 1:1 to receive either a single dose of IV amoxicillin/clavulanic acid or placebo within six hours after delivery. The authors excluded patients who had a clinical indication for ongoing antibiotic administration postpartum or who had a history of penicillin allergy or anaphylaxis to another beta-lactam agent. The primary outcome was confirmed or suspected maternal infection within six weeks of the delivery. Infection was defined as a new prescription for antibiotics for perineal wound-related infection, endometriosis, urinary tract infection with systemic features (i.e., pyelonephritis or sepsis), or other systemic infection.

There were 1,715 women randomized to the antibiotic group and 1,705 in the placebo group. Most of the births occurred using forceps (65%), while 35% were by vacuum extraction. The majority of the women (89%) underwent an episiotomy. The median time to receiving the antibiotic was 3.2 hours after delivery, and the median time to receiving the the placebo was 3.1 hours. Significantly fewer women randomized to the antibiotic group developed a confirmed or suspected infection (11%) compared to the placebo group (19%) (relative risk [RR], 0.58; 95% confidence interval (CI), 0.49-0.69; P < 0.0001). At six weeks after delivery, significantly more women in the antibiotic group reported less perineal pain, less use of pain medications, and less wound breakdown. There was no difference between the groups in the proportion of women who were breastfeeding, the reported dyspareunia, the length of hospital stay until discharge, the number of re-admissions, or the overall quality of life.

One woman in the placebo group reported a rash, and two women in the antibiotic group reported other allergic reactions, one of which was a serious adverse event. None of the women experienced anaphylaxis during the study. In a post-hoc analysis, the method of OVB did not have any impact on the primary outcome. Finally, at six weeks postpartum, the women who had received the antibiotic used fewer healthcare resources compared to those who had received placebo.

COMMENTARY

The study by Knight et al showed multiple benefits from a single dose of IV amoxicillin/clavulanic acid administered within six hours of OVB. Although there is never a convenient time for a patient to get an infection, certainly this is true for a mother dealing with a newborn. Indeed, a painful and infected perineum makes it very uncomfortable to sit and breastfeed. The decreased rate of infections in the antibiotic group, coupled with the low rate of adverse drug events, is compelling and may lead to changes in current guidelines and clinical practice.

OVB has been advocated by some experts as a way to decrease the number of cesarean deliveries. One drawback of OVB in the present study was that 89% of the women required an episiotomy. For many years, an episiotomy was believed to help prevent more extensive vaginal tearing during childbirth and to heal better than a natural tear. The procedure also was thought to help preserve the muscular and connective tissue support of the pelvic floor. However, research from the 1970s and 1980s disproved these assumptions, leading to a decline in the episiotomy rate from approximately 70% of all vaginal births to approximately 20% by 2000. Episiotomies carry an increased rate of infection, and the results from the study by Knight et al lend support to prescribing antibiotics in these cases.

The study had a few limitations. It was performed in a high-income setting, so the results might not be generalizable to low-income settings for which the rate of infection might be different. IV amoxicillin/clavulanic acid is not available in other countries, such as the United States, although IV ampicillin/sulbactam is similar and should cover the same spectrum of pathogens. Finally, patients with severe allergies were excluded and may have benefited from a different class of antibiotic.

Despite the strength of the findings, several unanswered questions remain. Does a single oral dose of amoxicillin/clavulanate work as well as IV amoxicillin/clavulanic acid? Is a single dose optimal or should multiple doses be prescribed? Would other antibiotics also be effective, such as for patients who are allergic to penicillin? Should an antibiotic be given prophylactically if OVB is anticipated? Should the antibiotic be given sooner than six hours after birth? Additional investigation is needed to clarify these and other issues. Until further investigation is done, no further evidence-based recommendations can be offered.