Prophylactic Antibiotics and Cesarean Section

Abstract & Commentary

By Alison Edelman, MD, MPH, Assistant Professor, Assistant Director of the Family Planning Fellowship Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, is Associate Editor for OB/GYN Clinical Alert.

Dr. Edelman reports no financial relationship to this field of study.

Synopsis: Comparison of antibiotic dosing prior to skin incision vs after cord clamping for prevention of post-cesarean infectious morbidity.

Source: Sullivan S, et al. Administration of cefazolin prior to skin incision is superior to cefazolin at cord clamping in preventing post cesarean infectious morbidity: a randomized, controlled trial. Am J Obstet Gynecol. 2007;196:455,e1-455.e5.

The title says it all in this randomized controlled trial by Sullivan and colleagues —"Administration of cefazolin prior to skin incision is superior to cefazolin at cord clamping in preventing post-cesarean infectious morbidity."1 This study compared the administration of prophylactic antibiotics (cefazolin) prior to skin incision (15-60 minutes) vs after cord clamping in women undergoing a non-emergent cesarean section with a gestational age greater than 24 weeks and no recent exposure to antibiotics. Women were monitored for evidence of infectious morbidity (endomyometritis, wound infection, and pyelonephritis) during their hospital stay and up to 6 weeks postpartum. Total infectious morbidity was decreased in the group that received antibiotics prior to skin incision [Relative Risk 0.4 (95% CI 0.18-0.87)]. The main reason for this decrease in infectious morbidity was due to fewer cases of endomyometritis [1% vs 5%; Relative Risk 0.2 (95% CI 0.2-0.94)] whereas the difference in wound infections was not statistically significant [3% vs 5%; Relative Risk 0.52 (95% CI 0.18-1.5)]. There were no differences in neonatal outcomes between the two groups (sepsis, septic workups, or NICU admissions).

Commentary

What evidence do we have for the use of prophylactic antibiotics for cesarean sections? A recent Cochrane Review2 provides us with the highest level of evidence (Level 1) for which antibiotics to use and for which cesarean sections to use them, but falls short on recommendations for timing. Prophylactic antibiotics used for cesarean sections in both non-laboring and laboring women have resulted in a significant decrease of post-cesarean fever, endomyometritis, urinary tract infection, and wound infection. A single dose of ampicillin or a first generation cephalosporin have similar efficacy at preventing post-cesarean infectious morbidity. No added benefit was found with broader spectrum antibiotics or multiple doses. Unfortunately due to lack of evidence, this review was unable to determine the optimal timing for administering prophylactic antibiotics.

Administration of antibiotics within one hour prior to skin incision is routine for surgeries requiring antibiotic prophylaxis, and, in fact is a JCAHO hospital quality improvement measure.3 So why does the practice of delaying prophylactic antibiotics until cord clamping exist with cesarean sections? The rationale given in the literature is the concern regarding neonatal exposure to antibiotics and adversely impacting a neonatal sepsis workup. However, no evidence exists to support these claims. In fact, data from animal and human studies have shown that adequate serum levels need to be present prior to bacterial exposure to prevent infection, that a delay in administration increases post-surgical infectious morbidity, and that no untoward neonatal effects have been proven to occur from the exposure.1,2,4-6

Until recently there were no studies sufficiently powered to determine a difference in infectious morbidity between antibiotics administered prior to incision vs after cord clamping. Two recent studies attempt to answer this question but their results are conflicting. In 2005, Thigpen, et al6 found no harm in giving prophylactic antibiotics but also found no difference in infectious morbidity with antibiotics administered prior to skin incision vs after cord clamping. This study had several key limitations, including the failure to achieve their desired sample size. In addition, a large number of women were already receiving antibiotics (penicillin) for GBS prophylaxis and the study population had overall higher rates of infectious morbidity. These limitations may have blunted the differences between groups.

In contrast, Sullivan, et al1 had a sample size adequate to determine differences in infectious morbidity between the two groups. This study excluded women who had recently received antibiotics (1 week or less) which, although not explicitly stated, most likely means women with chorioamnionitis and/or positive GBS cultures. The study did include women with diabetes and obesity; both of which can also increase the baseline risk for infection.7,8 In addition, cesarean sections were performed for a variety of indications (Stage 1 and 2 arrest, nonreassuring fetal status, scheduled). All in all, this study's findings appear to be valid and very generalizable to the general obstetrical population.

The most exciting studies to me are those that challenge our current standard of practice—the study by Sullivan et al is one such study. This study provides us with good but limited evidence to support dosing prophylactic antibiotics prior to skin incision in cesarean sections. More studies are needed to support these results, but at the very least women at high risk for post-cesarean infectious morbidity (ie, diabetes, obesity) should receive antibiotics prior to skin incision. Finally, the evidence is good, extensive, and consistent in regard to providing prophylactic antibiotics for all women undergoing cesarean section with either a single dose of ampicillin or first generation cephasporin.

References

  1. Sullivan S, et al. Administration of cefazolin prior to skin incision is superior to cefazolin at cord clamping in preventing postcesarean infectious morbidity: a randomized, controlled trial. Am J Obstet Gynecol. 2007;196:455,e1-455.e5.
  2. Hopkins L, Smaill F. Antibiotic prophylaxis regimens and drugs for cesarean section. [Systematic Review] Cochrane Pregnancy and Childbirth Group Cochrane Database of Systematic Reviews. 3, 2007.
  3. National hospital quality measures/the joint commission core measures. http://www.jointcommission.org. Accessed September 7, 2007.
  4. Burke JF. The effective period of preventative antibiotic action in experimental incisions and dermal lesions. Surgery. 1961;50:161-168.
  5. Classen DC, et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Eng J Med. 1992;326:281-286.
  6. Thigpen B, et al. Timing of prophylactic antibiotic administration in the uninfected gravida: a randomized clinical trial. Am J Obstet Gynecol. 2005;192:1864-1871.
  7. Myles TD, et al. Obesity as an independent risk factor for infectious morbidity in patients who undergo cesarean delivery. Obstet Gynecol. 2002;100:959-964.
  8. Diamond MP, et al. Increased risk of endometritis and wound infection after cesarean section in insulin-dependent diabetic women. Am J Obstet Gynecol. 1986;155:297-300.