by Jeff Minerd, Contributing Writer, MedPage TodaySeptember 20, 2017
A prophylactic, postoperative course of antibiotics with cephalexin (Keflex) and metronidazole (Flagyl) reduced rates of surgical site infection (SSI) in obese women undergoing cesarean delivery, a randomized clinical trial found.
Thirty days after C-section delivery, the rate of SSI was 6.4% in the treatment group versus 15.4% in the placebo group (between group difference 9%, 95% CI 2.9%-15%, P=0.01), reported Carri Warshak, MD, of the University of Cincinnati College of Medicine in Ohio, and colleagues.
The relative risk of SSI was reduced by 59% in the treatment group versus the placebo group (RR 0.41, 95% CI 0.22-0.77, P=0.01), they wrote in the Journal of the American Medical Association.
C-section deliveries are the most frequently performed surgeries in the U.S., Warshak's group said. Approximately 1.3 million were performed in 2010. Previous research has shown that 3% to 12% of all C-section deliveries are complicated by surgical site infections, and that infection risk increases with increasing maternal weight, they said.
"Obesity is an independent risk factor for SSI despite recommended preoperative antibiotic regimens. Limited studies have addressed optimal antibiotic regimens for the prevention of SSI among obese women," the investigators wrote. "Various postpartum antibiotic combinations and durations have been studied with conflicting benefit, but no studies have specifically addressed the obese population.
"This study was the first to our knowledge to evaluate the use of a prophylactic postcesarean course of cephalexin-metronidazole for prevention of SSI in an obese population," they said. "Cephalexin and metronidazole have high oral bioavailability and pharmacoeconomic advantages and are generally well tolerated, supporting the drug combination as a choice for postpartum prophylactic coverage."
Anatomic factors associated with obesity, such as skin folds and increased tissue pressure, or the bioactive qualities of adipose tissue, which secretes hormones, chemokines, and cytokines, may be why obesity increases SSI risk, the investigators said.
The single-center, double-blind study enrolled 403 pregnant women with a BMI≥ 30 and a final plan for C-section delivery. They were enrolled from October 2010 through December 2015 and followed through February 2016. Their mean age was 28 and mean BMI was 39.7.
Study participants were randomly assigned to receive oral cephalexin, 500mg, and metronidazole, 500mg (n=202), versus an identical-appearing placebo (n=201) every 8 hours for a total of 48 hours following C-section delivery. The primary outcome was SSI, defined as any superficial incisional, deep incisional, or organ/space infections within 30 days after C-section delivery.
All participants received 2 g of intravenous cefazolin (Ancef, Kefzol) prior to surgery, which was the standard of care at the time of the study. The overall SSI rate in the study was 10.9% (95% CI 7.9%-14%). No serious adverse events were reported in the treatment or placebo groups, the investigators said.
Cellulitis was the only secondary outcome significantly reduced with prophylactic antibiotics, Warshak's group reported. Cellulitis occurred in 12 participants in the treatment group (5.9%, 95% CI 2.7%-9.2%) versus 27 in the placebo group (13.4%, 95% CI 8.9%-18.2%). The mean difference was 7.5% (95% CI 1.7%-13.0%). The relative risk was 0.44 (95% CI 0.23-0.84). There were no significant differences between treatment and placebo for other secondary outcomes, including rates of incisional morbidity, fever of unknown etiology, wound separation, or endometritis.
In an accompanying editorial, David Calfee, MD, and Amos Grünebaum, MD, both of Weill Cornell Medicine in New York City, agreed with the authors' conclusions. "The results of this study suggest that a 2-day course of oral cephalexin and metronidazole after cesarean delivery may be an effective strategy to prevent postcesarean SSI among obese women," they wrote.
However, Calfee and Grünebaum added several caveats. "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," they said. "For example, were glycemic control, maintenance of normothermia, and preoperative bathing routinely implemented? Would the same benefit be seen among obese women who receive a higher preoperative dose of cefazolin (ie, 3 g), as recommended in current clinical practice guidelines?"
Both the editorialists and the authors said a chief study limitation was its single-center design, which raises the possibility of site-specific confounders, so that the results might not be generalizable to other obstetric practices.
The study was funded by the University of Cincinnati Department of Obstetrics and Gynecology.
Warshak and co-authors disclosed no relevant relationships with industry.
Calfee disclosed support from Merck, Sharpe, and Dohme.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner