Tara Haelle

January 27, 2017

LAS VEGAS — When obese women received a course of inexpensive antibiotics after cesarean delivery, surgical-site infections dropped by 60%, new research shows.

If this antibiotic strategy was implemented nationally, nearly 46,000 surgical-site infections and five maternal deaths would be prevented each year, at savings of more than $1 billion, investigators estimate.

"Even though the standard of care is to give antibiotics before the incision, in obese women, drug levels are lower," said lead investigator Carri Warshak, MD, associate professor of maternal–fetal medicine at the University of Cincinnati.

And with blood loss during cesarean delivery, "antibiotic blood levels are going to be even lower, and are basically gone by 4 hours after delivery," she told Medscape Medical News. At 4 hours, they're not healed and bacteria continue to get into the incision and uterus, especially in women with ruptured membranes."

Obese women make up a significant proportion of the 1.3 million annual cesarean deliveries. In fact, obesity complicates an estimated 30% to 40% of pregnancies, Dr Warshak reported.

An estimated 3% to 13% of all cesarean deliveries are complicated by surgical-site infections, and obese women are two to five times more likely to develop these infections.

High Risk for Infection

Here at the Society for Maternal-Fetal Medicine 2017 Annual Pregnancy Meeting, Dr Warshak presented results from a study that evaluated whether an extended course of antibiotics could reduce the rate of surgical-site infections in women with a body mass index (BMI) of at least 30 kg/m².

In the prospective, double-blind, randomized controlled trial, 192 women received cephalexin 500 mg plus metronidazole 500 mg administered orally every 8 hours for 48 hours and 190 received placebo.

The rate of tobacco use was high in both the antibiotic and placebo groups (27% vs 30%), as were rates of pregestational diabetes (16% vs 19%) and chronic hypertension (49% vs 51%). Average gestational age at delivery was 37.5 weeks in the two groups, and rates of multiples, primary cesarean, and pre-eclampsia were similar. All women received standard perioperative care, and the vast majority underwent low-transverse Pfannenstiel incision and suture skin closures.

The primary outcome was a surgical-site infection in the uterus or the incision. Secondary outcomes included any incision morbidity, cellulitis, endometritis, any fever, and wound separation.

Overall, the rate of surgical-site infection was 63% lower in the antibiotic group than in the placebo group. For the 119 women with ruptured membranes, it was 77% lower, and for the 264 women with intact membranes, it was 44% lower, although that difference was not significant. One woman included in this analysis had been excleded from the previous analysis because she no longer met the criteria for BMI.

Table 1. Rate of Surgical-Site Infections

Surgical-Site Infections Antibiotic Group, % Placebo Group, % Relative Risk
All women 6.8 16.3 0.37
Women with ruptured membranes 9.8 32.8 0.23
Women with intact membranes 5.3 9.2 0.56


Infections were more common in women with ruptured membranes than in those with intact membranes (21.3% vs 7.2%). The number needed to treat to prevent one infection was 10 overall, but for those with ruptured membranes, the number needed to treat was 4.

The only secondary outcome that was statistically significant was the 60% reduction in cellulitis, but decreases in the risk for endometritis and incisional morbidity approached significance.

Table 2. Secondary Outcomes

Outcome Antibiotic Group, % Placebo Group, % Relative Risk P Value
Cellulitis 6 14 0.40 .01
Endometritis 1 4 0.24 .05
Incisional morbidity 10 16 0.57 .07


In women with ruptured membranes, the risk for incisional morbidity was 59% lower in the antibiotic group than in the placebo group (P = .04), the risk for cellulitis was 74% lower (P = .01), and the risk for endometritis was a barely significant 77% lower (P = .05). In women with intact membranes, none of the differences in secondary outcomes were significant.

"This study is really important because we're the first to look specifically at the obese population and find strategies to decrease the risk for infection," coinvestigator Amy Valent, DO, a maternal–fetal medicine specialist at Oregon Health & Science University in Portland, told Medscape Medical News.

This study was underpowered to assess the effectiveness of antibiotics in subgroups, such as women with scheduled cesarean deliveries and those who had intact membranes and labored. In addition, it was limited because the high-risk population came from a single academic center and women with chorioamnionitis were excluded from the analysis.

"It's promising that an inexpensive oral antibiotic treatment appears to reduce risk, especially for women who have already ruptured their membranes," said Alison Stuebe, MD, associate professor of maternal–fetal medicine at the University of North Carolina at Chapel Hill.

"Women with BMIs over 30 mg/kg² are at high risk of wound complications, and we need new strategies to reduce their risk," she told Medscape Medical News. "However, I'm hesitant to make this a standard of care before we understand the implications for the maternal and infant microbiome. I'll want to see the published paper and additional work evaluating the potential adverse effects of 48 hours of antibiotics before I implement this regimen in practice."

Dr Stuebe added that "we're learning that the bacteria present in breast milk help to set up healthy bacteria in the baby's gut. It's possible that antibiotic treatment might affect the bacteria in mom's milk, with consequences for infant health. It's also not clear to what extent the oral antibiotics used in this study reduce infection risk, above and beyond azithromycin at time of cesarean, which was studied in the C/SOAP trial and is rapidly becoming standard care" (NCT01235546).

And there is concern about bacterial resistance. "I would have been equally happy if this study had shown no reduction so we could say don't give the antibiotics," Dr Warshak told Medscape Medical News, although she noted that one benefit of metronidazole is its lower propensity for the development of bacterial resistance.

However, when you have an intervention that can dramatically reduce infection in 15% to 20% of women, such as the ones in this study, "I think you have to consider it," she said.

Dr Warshak and Dr Valent have disclosed no relevant financial relationships. Dr Stuebe is a coinvestigator for a Janssen research and development study on perinatal depression.

Society for Maternal-Fetal Medicine (SMFM) 2017 Annual Pregnancy Meeting. Presented January 26, 2017.


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