From the Journals

Postsurgical antibiotics cut infection in obese women after C-section

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More antibiotics? Look before you leap

Despite the positive outcomes of this trial, it’s not yet time to tack on yet more antibiotics for every obese woman who undergoes a cesarean delivery, David P. Calfee, MD, and Amos Grünebaum, MD, wrote in an accompanying editorial (JAMA. 2017;318[11]:1012-3).

“When determining if and how the results of this study should alter current clinical practice, it is important to recognize that the results of this study are quite different from those of several previous studies conducted in other surgical patient populations in which no benefit from postoperative antimicrobial prophylaxis was found and on which current clinical guidelines for antimicrobial prophylaxis are based,” they wrote. “The explanation for this difference may be as simple as the identification in the current study of a very specific, high-risk group of patients for which the intervention is effective. However, several questions are worthy of additional consideration and study.”

For instance, the study was conducted over 5 years and may not reflect current practices for managing these patients, such as glycemic control and maintaining normothermia. Additionally, there may be additional risks to women that were not identified in the study, such as infection from antimicrobial-resistant pathogens.

Dr. Calfee and Dr. Grünebaum are at Weill Cornell Medical Center in New York. Dr. Calfee reported receiving grants from Merck, Sharp, and Dohme.



A 48-hour course of postoperative cephalexin and metronidazole, plus typical preoperative antibiotics, cut surgical site infections by 59% in obese women who had a cesarean delivery.

The benefit of the additional postoperative treatment was driven by a significant, 69% risk reduction among women who had ruptured membranes, Amy M. Valent, DO, and her colleagues reported (JAMA. 2017;318[11]:1026-34). However, the authors noted, “tests for interaction between the intact membranes and [ruptured] subgroups and postpartum cephalexin-metronidazole were not statistically different and should not be interpreted as showing a difference in significance or effect size among the subgroups with and without [rupture].”

Keeping that in mind, 12 obese women would need to be treated to avoid one surgical site infection, wrote Dr. Valent of the Oregon Health & Science University, Portland, and her coauthors.

The trial comprised 403 obese women who had a cesarean delivery. They were a mean of 28 years old. The mean body mass index was 40 kg/m2, and the mean subcutaneous adipose tissue thickness was about 3.4 cm. About a third of each treatment group was positive for Group B streptococcus; 31% had ruptured membranes at the onset of labor. More than 60% of women in both groups had a scheduled cesarean delivery.

All women had standard preoperative care, including skin prep with a chlorhexidine or povidone-iodine cleansing and an intravenous infusion of 2 g cefazolin. After delivery, they were randomized to placebo or to oral cephalexin 500 mg plus metronidazole 500 mg every 8 hours for 48 hours. The primary outcome was surgical site infection incidence within 30 days.

The overall rate of surgical site infection was 10.9% (44 women). Infections developed in 13 women in the active group and 31 in the placebo group (6.4% vs. 15.4%) – a significant difference, translating to a 59% risk reduction (relative risk, 0.41). Cellulitis was the only secondary outcome that was significantly reduced by prophylactic antibiotics, with infections occurring in 5.9% of the metronidazole-cephalexin group vs. 13.4% of the placebo group (RR, 0.44). The antibiotic regimen didn’t affect the other secondary endpoints, which included rates of incisional morbidity, endometritis, fever of unknown etiology, and wound separation.

The authors conducted a post-hoc analysis to examine the antibiotics’ effects on women who had ruptured and intact membranes at the time of delivery. The benefit was greatest among those with ruptured membranes. There were six infections among the active group and 19 among the placebo group (9.5% vs. 30.2%). This difference translated to a relative risk of 0.31 – a 69% risk reduction.

Among women with intact membranes, there were seven infections in the active group and 12 in the placebo group (5% vs. 8.7%). This translated to a 0.58 relative risk, which was not statistically significant.

“Interaction testing was performed between study groups (cephalexin-metronidazole vs. placebo) and by membrane status (intact vs. ruptured),” the authors noted. “The rate of surgical site infection was highest in those with [ruptured membranes] who received placebo (30.2%) and lowest in those with intact membranes who received antibiotics (5.0%), but the test for interaction did not show statistical significance at P = .30.”

There were no serious adverse events or allergic reactions reported for cephalexin or metronidazole. The authors noted that both drugs are excreted into breast milk in small amounts, but that no study has ever linked them with neonatal harm through breast milk exposure. However, they added, “Long-term childhood or adverse neonatal outcomes specific to cephalexin-metronidazole exposure cannot be determined, as outcome measures were not evaluated for this study protocol. Recognizing the maternal and neonatal benefit of breastfeeding, the lack of known neonatal adverse effects, and maternal reduction in [surgical site infection], the benefit of this antibiotic regimen likely outweighs the theoretical risks of breast milk exposure in the obese population.”

The University of Cincinnati Department of Obstetrics and Gynecology sponsored the trial. None of the authors reported any financial conflicts.

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