Antibiotic prophylaxis
Questions to consider regarding antibiotic prophylaxis for cesarean delivery include appropriateness of treatment, antibiotic(s) selection, timing of administration, dose, and special circumstances.
Should you give the patient prophylactic antibiotics?
Prophylactic antibiotics are justified for surgical procedures whenever 3 major criteria are met5:
- the surgical site is inevitably contaminated with bacteria
- in the absence of prophylaxis, the frequency of infection at the operative site is unacceptably high
- operative site infections have the potential to lead to serious, potentially life-threatening sequelae.
Without a doubt, all 3 of these criteria are fulfilled when considering either urgent or nonurgent cesarean delivery. When cesarean delivery follows a long labor complicated by ruptured membranes, multiple internal vaginal examinations, and internal fetal monitoring, the operative site is inevitably contaminated with hundreds of thousands of pathogenic bacteria. Even when cesarean delivery is scheduled to occur before the onset of labor and ruptured membranes, a high concentration of vaginal organisms is introduced into the uterine and pelvic cavities coincident with making the hysterotomy incision.6
In the era before prophylactic antibiotics were used routinely, postoperative infection rates in some highly indigent patient populations approached 85%.5 Finally, as noted previously, postcesarean endometritis may progress to pelvic abscess formation, septic pelvic vein thrombophlebitis, and septic shock; wound infections may be complicated by dehiscence and evisceration.
When should you administer antibiotics: Before the surgical incision or after cord clamping?
More than 50 years ago, Burke conducted the classic sequence of basic science experiments that forms the foundation for use of prophylactic antibiotics.7 Using a guinea pig model, he showed that prophylactic antibiotics exert their most pronounced effect when they are administered before the surgical incision is made and before bacterial contamination occurs. Prophylaxis that is delayed more than 4 hours after the start of surgery will likely be ineffective.
Interestingly, however, when clinicians first began using prophylactic antibiotics for cesarean delivery, some investigators expressed concern about the possible exposure of the neonate to antibiotics just before delivery—specifically, whether this exposure would increase the frequency of evaluations for suspected sepsis or would promote resistance among organisms that would make neonatal sepsis more difficult to treat.
Gordon and colleagues published an important report in 1979 that showed that preoperative administration of ampicillin did not increase the frequency of immediate or delayed neonatal infections.8 However, delaying the administration of ampicillin until after the umbilical cord was clamped was just as effective in preventing post‑cesarean endometritis. Subsequently, Cunningham and co-workers showed that preoperative administration of prophylactic antibiotics significantly increased the frequency of sepsis workups in exposed neonates compared with infants with no preoperative antibiotic exposure (28% vs 15%; P<.025).9 Based on these 2 reports, obstetricians adopted a policy of delaying antibiotic administration until after the infant’s umbilical cord was clamped.
In 2007, Sullivan and colleagues challenged this long-standing practice.10 In a carefully designed prospective, randomized, double-blind trial, they showed that patients who received preoperative cefazolin had a significant reduction in the frequency of endometritis compared with women who received the same antibiotic after cord clamping (1% vs 5%; RR, 0.2; 95% CI, 0.2–0.94). The rate of wound infection was lower in the preoperative antibiotic group (3% vs 5%), but this difference did not reach statistical significance. The total infection-related morbidity was significantly reduced in women who received antibiotics preoperatively (4.0% vs 11.5%; RR, 0.4; 95% CI, 0.18–0.87). Additionally, there was no increase in the frequency of proven or suspected neonatal infection in the infants exposed to antibiotics before delivery.
Subsequent to the publication by Sullivan and colleagues, other reports have confirmed that administration of antibiotics prior to surgery is superior to administration after clamping of the umbilical cord.10–12 Thus, we have come full circle back to Burke’s principle established more than a half century ago.7
Which antibiotic(s) should you administer for prophylaxis, and how many doses?
In an earlier review, one of us (PD) examined the evidence regarding choice of antibiotics and number of doses, concluding that a single dose of a first-generation cephalosporin, such as cefazolin, was the preferred regimen.5 The single dose was comparable in effectiveness to 2- or 3-dose regimens and to single- or multiple-dose regimens of broader-spectrum agents. For more than 20 years now, the standard of care for antibiotic prophylaxis has been a single 1- to 2-g dose of cefazolin.
Several recent reports, however, have raised the question of whether the prophylactic effect could be enhanced if the spectrum of activity of the antibiotic regimen was broadened to include an agent effective against Ureaplasma species.
Tita and colleagues evaluated an indigent patient population with an inherently high rate of postoperative infection; they showed that adding azithromycin 500 mg to cefazolin significantly reduced the rate of postcesarean endometritis.13 In a follow-up report from the same institution, Tita and co-workers demonstrated that adding azithromycin also significantly reduced the frequency of wound infection.14 In both of these investigations, the antibiotics were administered after cord clamping.
In a subsequent report, Ward and Duff15 showed that the combination of azithromycin plus cefazolin administered preoperatively resulted in a very low rate of both endometritis and wound infection in a population similar to that studied by Tita et al.13,14
Very recently, Tita and associates published the results of the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial conducted at 14 US hospitals.16 This study included 2,013 women undergoing cesarean delivery during labor or after membrane rupture who were randomly assigned to receive intravenous azithromycin 500 mg (n = 1,019) or placebo (n = 994). All women also received standard antibiotic prophylaxis with cefazolin. The primary outcome (a composite of endometritis, wound infection, or other infection within 6 weeks) was significantly lower in the azithromycin group than in the placebo group (6.1% vs 12.0%, P<.001). In addition, there were significant differences between the treatment groups in the rates of endometritis (3.8% in the azithromycin group vs 6.1% in the placebo group, P = .02) as well as in the rates of wound infection (2.4% vs 6.6%, respectively, P<.001). Of additional note, there were no differences between the 2 groups in the composite neonatal outcome of death and serious neonatal complications (14.3% vs 13.6%, P = .63).The investigators concluded that extended-spectrum prophylaxis with adjunctive azithromycin safely reduces infection rates without raising the risk of neonatal adverse outcomes.