Two antibiotics before cesarean delivery reduce infection rates further than one agent
Tita AT, Szychowski JM, Boggess K, et al; for the C/SOAP Trial Consortium. Adjunctive azithromycin prophylaxis for cesarean delivery. N Engl J Med. 2016;375(13):1231-1241.
Tita and colleagues reported the results of a multicenter trial that was designed to assess whether a combination of 2 antibiotics, including one that specifically targets ureaplasma species, provided more effective prophylaxis against postcesarean infection than single-agent prophylaxis.
Details of the study
The Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial was conducted at 14 centers in the United States and included 2,013 women who were at least at 24 weeks' gestation and who had a cesarean delivery during labor or after membrane rupture.
The authors randomly assigned 1,019 women to receive 500 mg of intravenous azithromycin plus conventional single-agent prophylaxis (usually cefazolin) and 994 women to receive a placebo plus conventional prophylaxis. The primary outcome was the composite of endometritis, wound infection, or other infection occurring within 6 weeks.
The authors observed that the primary outcome occurred in 62 women (6.1%) who received azithromycin plus conventional prophylaxis and in 119 women (12%) who received only single-agent prophylaxis. The relative risk of developing a postoperative infection was 0.51 in women who received the combined therapy. There were significant differences between the 2 groups in both the rates of endometritis (3.8% vs 6.1%, P = .02) and wound infection (2.4% vs 6.6%, P<.001). There were no differences between the groups in the frequency of the secondary neonatal composite outcome, which included neonatal death and serious neonatal complications.
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Preventing infection after cesarean delivery: 5 more evidence-based measures to consider
Efficacy of dual-agent prophylaxis
At present, the standard of care is to administer prophylactic antibiotics to all women having cesarean delivery, including women having a scheduled cesarean in the absence of labor or ruptured membranes. Multiple studies have shown clearly that prophylaxis reduces the frequency of endometritis and, in high-risk patient populations, wound infection, and that prophylaxis is most beneficial when administered prior to the time the surgical incision is made. The most commonly used drug for prophylaxis is cefazolin, a first-generation cephalosporin. The usual recommended dose is 2 g, administered immediately prior to surgery.3,4
Although most centers in the United States traditionally have used just a single antibiotic for prophylaxis, selected recent reports indicate that expanding the spectrum of activity of prophylactic antibiotics can result in additional beneficial effects. Specifically, Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection.5 They showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis. In a follow-up report from the same institution, Tita and colleagues demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.6 Of note, in both these investigations, the antibiotics were administered after cord clamping. In a subsequent report, Ward and Duff showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a combined rate of endometritis and wound infection that was less than 3%.7
Related article:
Preventing infection after cesarean delivery: Evidence-based guidance
C/SOAP trial confirmed lower infection rates with combined regimen
Results of the present study confirm the findings of these 3 investigations. The trial included a large sample size. The study was carefully designed, and the end points were clearly defined. It included only patients at increased risk for postoperative infection by virtue of being in labor or having ruptured membranes at the time of cesarean delivery. Patients who received standard prophylaxis, usually cefazolin, plus azithromycin had a significantly lower risk of postcesarean endometritis and wound infection compared with patients who received a single antibiotic. The overall risk of infection was reduced by an impressive 50%.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Based on the results of the C/SOAP trial, considered in conjunction with the 3 previously cited investigations,5-7 we believe that the standard approach to antibiotic prophylaxis should be to administer both cefazolin, in a dose of 2 g, plus azithromycin, in a dose of 500 mg, prior to surgery. Cefazolin can be administered as an intravenous bolus; azithromycin should be administered as a continuous infusion over a 60-minute period prior to surgery. Clinicians may anticipate very low rates of both endometritis and wound infection with this regimen.