Antimicrobial Prophylaxis for Cesarean Delivery - Timing of Administration

Antimicrobial prophylaxis for cesarean delivery has been a general practice for cesarean deliveries because it significantly reduces postoperative maternal infectious morbidity (1). These antibiotics have been administered intraoperatively after umbilical cord clamping for two theoretic concerns related to the fetus: 1) antibiotics in neonatal serum may mask newborn positive bacterial culture results; and 2) fetal antibiotic exposure could lead to an increase in newborn colonization or infection with antibiotic-resistant organisms. Recently, several randomized clinical trials investigated the timing of antimicrobial prophylaxis for cesarean delivery (2–4).

Surgical research data support antimicrobial prophylaxis administration, ideally within 30 minutes and certainly within 2 hours of the time of skin incision, to prevent surgical site infection (5). In one study, 1.4% of patients who received perioperative antimicrobial prophylaxis within 3 hours after skin incision had wound infections, versus 0.6% of patients who were given preoperative prophylaxis in the 2 hours before skin incision (5). The infusion should be timed so that a bactericidal serum level is established by the time of skin incision, and to maintain therapeutic levels throughout the operation (6). For longer surgical procedures, readministration of the drug is indicated at intervals of one or two times the half-life of the drug (using the same dose) (7). Narrow-spectrum antibiotics that are effective against gram-positive bacteria, gram-negative bacteria, and some anaerobic bacteria, such as a first-generation cephalosporin, are mainly used for prophylaxis for cesarean delivery. After a single 1 gram intravenous dose of cefazolin, a therapeutic level is maintained for approximately 3–4 hours. A larger dose may be indicated if a woman is obese. For women with a significant allergy to β-lactam antibiotics, such as cephalosporins and penicillins, clindamycin with gentamicin is a reasonable alternative.

In a 2007 randomized, controlled trial designed toexamine maternal infectious morbidity rates after cesarean delivery, 175 and 182 women received antibiotics preoperatively and after umbilical cord clamping, respectively (2). This study included both laboring and nonlaboring women. The administration of cefazolin (1 g, intravenously) 15–60 minutes before cesarean delivery (preoperative group) was associated with a significant reduction of endometritis of 1% compared with a rate of 5% in women who received the same medication after umbilical cord clamping (cord-clamp group) (2). There was no significant difference in the rates of postoperative wound infections in the two treatment groups. Overall, the total postoperative infection rates were decreased significantly from 11.5% to 4.5% in the preoperative group compared with the cord-clamp group. There were no differences in the rates of neonatal sepsis, neonatal intensive care unit admission, or neonatal sepsis due to resistant organisms, although the study was not designed with sufficient power to address these secondary outcomes.

In 2005, another randomized controlled trial evaluated the administration of cefazolin (2 g, intravenously) at the time of skin incision (at-incision group) compared with administration after umbilical cord clamping in women in labor undergoing cesarean delivery (cord-clamping group) (3). The investigators observed a significant decrease in endometritis (7.8% versus 14.8% in the at-incision group and the cord-clamping group, respectively), but not wound infection (3.9% versus 5.4% in at-incision group and cord-clamping group, respectively) (3). The initial power analysis for this study suggested that 270 women per group were needed, but the interim analysis determined a need for only 150 per group; therefore, the study was stopped with 153 and 149 women per group for the at-incision and cord-clamping groups, respectively. In addition, the infection rates for both groups in this study were three times higher than in the 2007 study. There were no differences in rates of neonatal intensive care unit admission, neonatal sepsis, or suspected sepsis between the groups although this study also was underpowered for evaluation of these secondary outcomes. The only other randomized trial examining cefazolin was smaller (90 patients), and found no significant difference in maternal infectious outcome (4). These investigators observed similar rates of endometritis (2% versus 2.4% in the preoperative antibiotic group and the after-cord-clamping group, respectively) and wound infection (2% versus 4.9% in preoperative antibiotic group and after-cord-clamping group, respectively) (4, 8).

From these data, it would appear that preoperatively administered antimicrobial prophylaxis does not appear to have any deleterious effects on mother or neonate. Preoperative administration significantly reduces endometritis and total maternal infectious morbidity compared with administration of antibiotics after umbilical cord clamping (8). These data further suggest that preoperative antimicrobial prophylaxis for cesarean delivery is not associated with an increase in neonatal infectious morbidity or the selection of antimicrobial resistant bacteria causing neonatal sepsis. However, because the studies were not powered to analyze those outcomes, additional prospective evaluation is warranted.

The Committee on Obstetric Practice recommends antimicrobial prophylaxis for all cesarean deliveries unless the patient is already receiving appropriate antibiotics (eg, for chorioamnionitis) and that prophylaxis should be administered within 60 minutes of the start of the cesarean delivery. When this is not possible (eg, need for emergent delivery), prophylaxis should be administered as soon as possible.

References

1. Smaill FM, Gyte GM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD007482. DOI: 10.1002/14651858.CD007482.pub2.
2. Sullivan SA, Smith T, Chang E, Hulsey T, Vandorsten JP, Soper D. Administration of cefazolin prior to skin incision is superior to cefazolin at cord clamping in preventing postcesarean infectious morbidity: a randomized, controlled trial [published erratum appears in Am J Obstet Gynecol 2007;197:333]. Am J Obstet Gynecol 2007;196:455.e1–455.e5.
3. Thigpen BD, Hood WA, Chauhan S, Bufkin L, Bofill J, Magann E, et al. Timing of prophylactic antibiotic administration in the uninfected laboring gravida: a randomized clinical trial. Am J Obstet Gynecol 2005;192:1864-8; discussion 1868–71.
4. Wax JR, Hersey K, Philput C, Wright MS, Nichols KV, Eggleston MK, et al. Single dose cefazolin prophylaxis for postcesarean infections: before vs. after cord clamping. J Matern Fetal Med 1997;6:61–5.
5. Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL,Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992;326:281–6.
6. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1999;20:250-78; quiz 279–80.
7. Page CP, Bohnen JM, Fletcher JR, McManus AT, Solomkin JS,Wittmann DH. Antimicrobial prophylaxis for surgical wounds. Guidelines for clinical care [published erratumappears in Arch Surg 1993;128:410]. Arch Surg 1993;128:79–88.
8. Costantine MM, Rahman M, Ghulmiyah L, Byers BD, Longo M, Wen T, et al. Timing of perioperative antibiotics for cesarean delivery: a metaanalysis. Am J Obstet Gynecol 2008;199:301.e1–301.e6.