Conference Coverage

VIDEO: Dual antibiotic prophylaxis cuts cesarean SSIs


 

AT THE PREGNANCY MEETING

– Two days of prophylaxis with two oral antibiotics cut the surgical site infection rate by more than half in a randomized trial with more than 400 obese women who had cesarean deliveries.

The protective effect from combined treatment with cephalexin and metronidazole was especially powerful in the most at-risk patients, women with ruptured membranes before cesarean surgery. In this subgroup prophylaxis with the two antibiotics for 2 days cut surgical site infections (SSIs) during the 30 days after surgery, from a rate of 33% in control women who received placebo to a 10% rate, a 77% relative risk reduction that was statistically significant, Carri R. Warshak, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal and Fetal Medicine.

“I am very excited that we found a way to help the kinds of women in the study, very-high-risk women, with an effective way to reduce their risk of infection,” Dr. Warshak of the University of Cincinnati said in a video interview. The obese women enrolled in the study, especially those with ruptured membranes, “have a very high risk of morbidity, so it’s very exciting that we found a way to help prevent” SSIs.

Dr. Elliott Main

Dr. Elliott Main

For obese women, especially those with other risk factors, SSIs following cesarean delivery are a really big deal. These data warrant giving this strategy serious consideration,” commented Elliott Main, MD, medical director of the California Maternal Quality Care Collaborative in Stanford.

“Our study is the first to target postpartum interventions to reduce SSIs specifically in this high-risk population” of obese mothers, said Amy M. Valent, DO, a maternal fetal medicine clinician at Oregon Health & Science University in Portland, who ran the trial with Dr. Warshak.

The trial randomized women with a body mass index of at least 30 kg/m2 who underwent a planned or unplanned cesarean delivery at the University of Cincinnati during 2010-2015. Following standard management during cesarean delivery, the women received either 500 mg oral cephalexin and 500 mg oral metronidazole or placebo every 8 hours for 48 hours following delivery. The primary outcome was the incidence of SSIs, and randomization was stratified so that similar numbers of women with ruptured membranes got into each treatment arm. The enrolled women averaged 28 years of age, and average BMI was about 40 kg/m2. Nearly a third of the women had ruptured membranes at the time of surgery, more than a quarter of the enrolled women used tobacco, and more than a fifth had preeclampsia.

Dr. Amy M. Valent, a maternal fetal medicine clinician at Oregon Health & Science University in Portland Mitchel L. Zoler/Frontline Medical News

Dr. Amy M. Valent

The 30-day incidence of postpartum SSIs was 7% in 192 evaluable women who received oral prophylaxis and 16% in 190 evaluable women in the placebo group, a statistically significant difference that computes to a number needed to treat of 10 to prevent one SSI, Dr. Warshak reported. Among women with ruptured membranes, four needed to receive this prophylaxis to prevent one SSI. The prophylaxis also linked with a statistically significant 60% reduction in the rate of cellulitis and a 76% relative reduction in endometritis that fell just short of statistically significance.

Additional analyses reported at the meeting by Dr. Valent showed that other risk factors that significantly boosted the rate of SSIs were labor prior to delivery, use of internal monitoring, and operative time of more than 90 minutes. Antibiotic prophylaxis was able to significantly reduce SSI rates in women with any of these additional risk factors, compared with placebo. A cost effectiveness analysis she ran estimated that if the antibiotic prophylaxis tested in the study were used on the roughly 460,000 obese U.S. women having cesarean deliveries annually, it would be cost saving as long as the antibiotic regimen cost no more than $357 a person. Factoring in the SSIs and long-term morbidity that prophylaxis would prevent, and the quality-adjusted life-years it would add, showed that prophylaxis would be cost-effective up to a cost of $33,557 per woman.

The prophylaxis carries a “relatively low cost and is easy to use,” Dr. Valent said.

Safety of the antibiotic combination was a question raised by Laura E. Riley, MD, director of ob.gyn. infectious disease and labor and delivery at Massachusetts General Hospital in Boston. “My biggest concern is 48 hours of these antibiotics,” and whether prophylaxis could be achieved with fewer doses, she said in an interview. “I’d want to minimize the dosage, and also try other, nondrug approaches to minimizing SSI risk in obese women.”

Dr. Laura E. Riley, director of ob.gyn. infectious disease and labor and delivery at Massachusetts General Hospital in Boston Mitchel L. Zoler/Frontline Medical News

Dr. Laura E. Riley

But Dr. Warshak insisted that the 48-hour regimen of cephalexin and metronidazole was well tolerated and posed little risk. She noted that only 8 women in the entire study group of 403 stopped taking their medication once treatment began, and the most common reason for stopping was nausea associated with the large size of the pills (both active drug and placebo). The two adverse events that occurred, preeclampsia and pulmonary embolism, were not treatment related, and there were no allergic reactions to the drugs. “This is a very widely available and well-tolerated regimen,” she said. The study protocol excluded patients with known allergies to either drug, and all patients in the trial received standard intraoperative prophylaxis with cefazolin, which would have revealed a previously unknown cephalosporin allergy.

“I wouldn’t say that universally, every obstetrical program should do this, but clinicians should look at the comorbidities their mothers have and their SSI rates. There are populations out there at lower risk, but there are also populations like ours, with a SSI rate of 10%-20%,” Dr. Warshak said.

She also acknowledged that even her own obstetrical group in Cincinnati needs to now reach a consensus on an appropriate strategy for expanded cesarean-delivery prophylaxis. That’s because a 2016 report from a large, randomized trial documented another successful strategy for limiting infections following cesarean delivery: a preoperative intravenous dose of azithromycin as a supplement to standard cefazolin. The Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial, done in women with any BMI but specifically nonelective cesarean deliveries, showed a significant reduction in the combined rate of SSIs, endometritis, or any other infection during 6 weeks of follow-up among women who received azithromycin on top of standard prophylaxis (N Engl J Med. 2016 Sept 29;375[13]:1231-41).

“The bottom line is that, a couple of grams of cefazolin [administered before the incision] isn’t enough, especially for women with risk factors for infection. We see infection rates of more than 10% because cefazolin alone is simply inadequate. The results from both our study and the 2016 study show we can do better to reduce morbidity,” said Dr. Warshak.

“In high-risk women, such as those who are obese, we probably need to expand the spectrum and duration of prophylaxis,” agreed Dr. Main. “Obesity is one high-risk group, but there are others.”

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