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Maternal-Fetal Medicine

Antibiotic Prophylaxis for Cesarean Delivery: Evolving Practices

Dana Figueroa, MD; Alan T. N. Tita, MD, PhD

Prevention of infection after cesarean delivery is critical to reduce complications in the obstetric patient. Antibiotics given prior to surgery may be safe and more effective than those administered at the time of incision or postpartum.

Infection is a leading cause of pregnancy-related morbidity and mortality. Women who deliver by cesarean have a 5- to 20-fold higher risk for postpartum infection.1 Cesarean delivery (CD) is the most common major surgical procedure in the United States, with more than 1.3 million performed annually. Considering the increasing CD rate (expected to attain 50% of all US deliveries in the next decade if the trend continues unabated), the burden of postcesarean surgical site infections is expected to rise.2 The use of antibiotic prophylaxis during CD is a proven cost-effective strategy to prevent postcesarean infections. We present a synopsis of established and newly evolving standards for antibiotic prophylaxis for CD.

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ESTABLISHED STANDARDS

The use of prophylactic antibiotics (compared to placebo) significantly reduces the risk for most common postcesarean infections, endometritis, and wound infection by approximately 50% to 60%.1 The risks for fever and more severe maternal infections (including bacteremia, septic shock, septic pelvic thrombophlebitis, necrotizing fasciitis, pelvic abscess) and death due to infection are also reduced by about 50%. These benefits are true for both elective (scheduled) and nonelective (emergent or laboring) CDs.

A single dose of antibiotics is as effective as multiple-dose regimens and, theoretically, is less likely to result in resistant infections, including pseudomembranous colitis. Narrow-spectrum antibiotics, such as ampicillin or cefazolin, are the most commonly studied effective regimens.1 However, because of increasing resistance to ampicillin, ACOG recommends a single dose of a first-generation cephalosporin such as cefazolin (typically, 1 or 2 g given intravenously).3 Recently, evolving practices regarding the use of antibiotic prophylaxis for CD have focused on 2 emerging concepts: (1) the timing of administration and (2) the use of extended-spectrum regimens (a second antibiotic of a different class in addition to the standard cephalosporin).2

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TIMING OF ANTIBIOTIC PROPHYLAXIS

placental exposure of fetuses when given earlier, antibiotic prophylaxis for CD has classically been administered after clamping the umbilical cord.2 However, research in nonpregnant populations undergoing surgery and recent studies involving pregnant women have suggested that administration of antibiotics prior to incision (ideally 30 to 60 minutes before, to allow for optimal concentration at the surgical site) may further reduce infection by about 50% compared to administration during surgery or after umbilical cord clamp.2,4-8 Moreover, these studies have suggested no increase in adverse neonatal outcomes, including the need for sepsis work-ups and NICU admission.5,8 Anecdotal evidence indicates that many obstetric providers in the United States are adopting a policy of preincision antibiotic prophylaxis as the standard of care for CDs and other surgeries. However, the most recent Cochrane review reported similar effectiveness when antibiotics were administered prior to incision or after umbilical cord clamp. Additional studies evaluating the effects of antibiotic exposure on the neonate and the impact on resistant infections were recommended.1

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EXTENDED-SPECTRUM ANTIBIOTIC PROPHYLAXIS

Postcesarean infections are polymicrobial. Ureaplasma urealyticum is one of the most common microbes isolated from these infections. In addition, the recovery of Ureaplasma from cultures of the chorioamnion obtained at CD is a risk factor for subsequent postcesarean infection. Based on these observations, the addition of azithromycin—which provides specific coverage against Ureaplasma—to the standard cephalosporin has been evaluated.9 Similarly, because bacterial vaginosis has been associated with up to a 6-fold increase in postcesarean infections, the addition of metronidazole (500 mg intravenously or 5 g vaginally) has also been evaluated.

These extended-spectrum regimens have been shown to reduce postcesarean infection by 30% to 60% and to shorten hospital stay compared to single-agent narrow-spectrum antibiotics.2,9 These antibiotics were typically administered after umbilical cord clamp or surgical incision; it is unknown whether extended-spectrum prophylaxis prior to incision confers any benefits over cefazolin alone prior to incision. Thus, compared to evolving practices toward increased use of preincision antibiotic prophylaxis, fewer obstetric providers appear to have adopted extended-spectrum protocols.

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Summary

Intravenous administration of a narrow-spectrum antibiotic, commonly a first-generation cephalosporin, is a well-established standard for the prevention of postcesarean infection. Administration of antibiotic prophylaxis prior to incision (ideally, 30 to 60 minutes before), as opposed to after umbilical cord clamp, has been shown in a number of recent studies to be associated with lower rates of infection.

The use of extended-spectrum regimens, comprising azithromycin or metronidazole in addition to cefazolin, may be associated with lower rates of infection compared to cefazolin alone given after cord clamp. Additional studies are needed to confirm the superiority of preincision protocols, with and without extended regimens, and their impact on the neonate, as well as to monitor for the possible emergence of resistant organisms.

The authors report no actual or potential conflicts of interest in relation to this article.

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Dana Figueroa, MD, is Clinical Instructor and Fellow, and Alan T. N. Tita, MD, PhD, is Assistant Professor, both at the Center for Women’s Reproductive Health, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Alabama at Birmingham.

References

1. Smaill FM, Gyte GM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev. 2010;(1):CD007482.
2. Tita AT, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW. Emerging concepts in antibiotic prophylaxis for cesarean delivery: a systematic review. Obstet Gynecol. 2009;113(3):675-682.
3. American College of Obstetricians and Gynecologists. ACOG practice bulletin number 47, October 2003: Prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2003;102(4):875-882.
4. 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(5):281-286.
5. 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. Am J Obstet Gynecol. 2007;196(5):455.e1-e5.
6. Kaimal AJ, Zlatnik MG, Cheng YW, et al. Effect of a change in policy regarding the timing of prophylactic antibiotics on the rate of postcesarean delivery surgical-site infections. Am J Obstet Gynecol. 2008;199(3):310.e1-e5.
7. Owens SM, Brozanski BS, Meyn LA, Wiesenfeld HC. Antimicrobial prophylaxis for cesarean delivery before skin incision. Obstet Gynecol. 2009;114(3):573-579.
8. Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean delivery: a metaanalysis. Am J Obstet Gynecol. 2008;199(3):301.e1-e6.
9. Andrews WW, Hauth JC, Cliver SP, Savage K, Goldenberg RL. Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis. Obstet Gynecol. 2003;101(6):1183-1189.

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