Obstetrics & Gynecology:
Perioperative Antibiotic Prophylaxis for Nonlaboring Cesarean Delivery
Dinsmoor, Mara J. MD, MPH; Gilbert, Sharon MS, MBA; Landon, Mark B. MD; Rouse, Dwight J. MD; Spong, Catherine Y. MD; Varner, Michael W. MD; Caritis, Steve N. MD; Wapner, Ronald J. MD; Sorokin, Yoram MD; Miodovnik, Menachem MD; O’Sullivan, Mary J. MD; Sibai, Baha M. MD; Langer, Oded MD; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
From the Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois; the Ohio State University, Columbus, Ohio, the University of Alabama at Birmingham, Birmingham, Alabama; the University of Utah, Salt Lake City, Utah; the University of Pittsburgh, Pittsburgh, Pennsylvania; Thomas Jefferson University, Philadelphia, Pennsylvania; Wayne State University, Detroit, Michigan; the University of Cincinnati, Cincinnati, Ohio; the University of Miami, Miami, Florida; the University of Tennessee, Memphis, Tennessee; the University of Texas at San Antonio, San Antonio, Texas; the George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
*For a list of other members of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Maryland, see the Appendix online at http://links.lww.com/AOG/A126.
Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, and HD36801).
The authors thank Francee Johnson, BSN, and Julia Gold, RN, for protocol development and coordination between clinical research centers, and Elizabeth Thom, PhD, for protocol/data management and statistical analysis.
Presented in poster format at the 54th Annual Meeting of the Society for Gynecologic Investigation, Reno, Nevada; March 15–17, 2007.
Corresponding author: Mara J. Dinsmoor, MD, MPH, Department of Obstetrics and Gynecology, Feinberg School of Medicine of Northwestern University, NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen Building, Suite 1507, Evanston, IL 60201; e-mail: email@example.com.
Financial Disclosure The authors did not report any potential conflicts of interest.
OBJECTIVE: To estimate the efficacy of antibiotic prophylaxis at the time of nonlaboring cesarean delivery in reducing postpartum infection-related complications.
METHODS: We performed a secondary analysis of an observational study of cesarean deliveries performed at 13 centers from 1999–2000. Patients were included if they had cesarean delivery before labor, did not have intrapartum infection, and were not given antibiotics at delivery for reasons other than prophylaxis. The occurrence of postpartum endometritis, wound infection, and other, less common infection-related complications was compared between those who did and did not receive antibiotic prophylaxis. Results were adjusted for smoking, payer status, gestational age and body mass index at delivery, race, diabetes, antepartum infections, presence of anemia, operative time, type of cesarean delivery (primary or repeat), and center.
RESULTS: Of the 9,432 women who met study criteria, the 6,006 (64%) who received antibiotic prophylaxis were younger, heavier at delivery, and were more likely to be African American, receive public insurance, and have diabetes. Patients who received antibiotic prophylaxis were less likely to develop postpartum endometritis (121 [2.0%] compared with 88 [2.6%], adjusted odds ratio [OR] 0.40, 95% confidence interval [CI] 0.28–0.59) or wound infection (31 [0.52%] compared with 33 [0.96%], adjusted OR 0.49, 95% CI 0.28–0.86).
CONCLUSION: Antibiotic prophylaxis at the time of nonlaboring cesarean delivery significantly reduces the risks of postpartum endometritis and wound infection.
LEVEL OF EVIDENCE: III
Women delivering by cesarean are at a fivefold to 30-fold increased risk of postpartum infection-related complications compared with those delivering vaginally.1,2 Women undergoing cesarean delivery before labor or membrane rupture are at much lower risk of infection-related complications than those having cesarean delivery during labor, in which the risk of postpartum infection (without antibiotic prophylaxis) is as high as 45–85% in some populations.3,4 The efficacy of perioperative antibiotics in reducing infection-related complications after cesarean deliveries performed in laboring women has been documented in a number of studies. In these patients, the use of perioperative antibiotics reduces the risk of postpartum endometritis by 75%, the risk of wound infection by 65%, and also may decrease the risk of urinary tract infection.5 The efficacy of perioperative antibiotics at the time of elective (nonlaboring) cesarean delivery is not as well-studied, and antibiotic prophylactic practices vary widely. The American College of Obstetricians and Gynecologists recently has recommended that antibiotic prophylaxis be administered to all women undergoing cesarean delivery.6 In this study, we sought to estimate the efficacy of antibiotic prophylaxis at the time of nonlaboring cesarean delivery in reducing postpartum infection-related complications.
MATERIALS AND METHODS
This study is a secondary analysis of a prospectively collected database of all cesarean deliveries performed between January 1, 1999, and December 31, 2000, in 13 academic centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The original study was approved by the participating institutions’ institutional review boards. Data were collected on demographic characteristics, medical and obstetric history, course of labor and delivery, short term neonatal outcomes, and intraoperative and postoperative maternal complications. The use and type of antibiotics and the indication for the antibiotics was recorded. All interventions, including administration, timing, and type of antibiotics given, were at the discretion of the delivering physician.
Only those women who had cesarean delivery before the onset of labor were included. Women delivering preterm (before 37 weeks of gestation) were excluded, as were women who had an active infection during the pregnancy or at delivery (for example, pyelonephritis, pneumonia, cervicovaginal infection, or clinical chorioamnionitis). Women who received perioperative antibiotics for indications other than surgical antibiotic prophylaxis (for example, subacute bacterial endocarditis prophylaxis and group B streptococcus prophylaxis) were not included. Women who were colonized with group B streptococcus but who were not given group B streptococcus prophylaxis before delivery were not excluded. Additional analyses that excluded those women with spontaneous rupture of the membranes (ie, rupture of the membranes before performing the cesarean delivery) also were performed.
The occurrence of postpartum endometritis, wound infection, and other less common infection-related complications was compared between those who did and did not receive antibiotic prophylaxis. For the purposes of this study, postpartum endometritis was defined as a postpartum temperature of 38°C (100.5°F) or higher with receipt of postpartum antibiotics and the clinical diagnosis of postpartum endometritis. The clinical diagnosis of postpartum endometritis was based on the presence of abnormal uterine tenderness in the absence of other clinical or laboratory findings suggestive of another source of infection. The diagnosis of a wound infection was based on chart review of clinical criteria, specifically erythema of the incision accompanied by purulent drainage that required wound care. Other infections that were recorded included maternal sepsis, fascial dehiscence or evisceration, necrotizing fasciitis, pelvic abscess, and septic pelvic thrombophlebitis.
Statistical analysis included the Wilcoxon rank-sum test for continuous variables and the χ2 test for categorical variables. Multivariable logistic regression analyses were performed on three outcomes, adjusting for variables that were significantly different on the univariable analysis and were felt to be clinically relevant differences or were suspected risk factors for infection-related outcomes. For the regression analysis, dichotomization of the center of enrollment was based on whether the center predominately administered intrapartum antibiotics prophylactically. The confidence interval (CI) for number needed to treat was calculated using the Wilson score method.7 Nominal two-tailed P values were reported, with statistical significance considered as P<.05. No adjustment was made for multiple comparisons. SAS software (SAS Institute, Inc., Cary, NC) was used for analysis.
Of the 9,432 women who underwent primary or repeat cesarean delivery before labor and who met our inclusion criteria, 6,006 (64%) received perioperative antibiotic prophylaxis. Use of prophylactic antibiotics for women undergoing cesarean delivery before labor varied widely between centers, ranging from 13% to 98%. Of those women who received prophylactic antibiotics, 5,257 (87.5%) received only a cephalosporin, 401 (6.7%) received only a broad-spectrum penicillin, seven (0.1%) received both, and the remaining women (341, 5.7%) received another type of primary antibiotic for surgical prophylaxis. Eighty-five women (1.4%) received more than one antibiotic for surgical prophylaxis.
Demographic characteristics are shown in Table 1. Women who received antibiotic prophylaxis were younger and heavier at delivery and were more likely to be African American and to receive public insurance. Antepartum complications including diabetes, anemia (most recent hemoglobin before delivery of less than 10 g/dL), and antepartum infection (remote from delivery) were also more common in the prophylaxis group (Table 2). The indications for cesarean delivery are listed in Tables 3 and 4. Although some obstetric outcomes were statistically significantly different between the two populations, including gestational age at delivery, birth weight, and operative time, these differences likely are not clinically significant (Tables 1 and 5).
After adjusting for smoking, payer status, gestational age and body mass index at delivery, race, diabetes, antepartum infections, anemia, operative time, primary or repeat cesarean delivery, and study center, multivariate analyses revealed that the use of prophylactic antibiotics resulted in a significant reduction in the rates of postpartum endometritis (adjusted odds ratio [OR] 0.40, 95% CI 0.28–0.59) and wound infection (adjusted OR 0.49, 95% CI 0.28–0.86). Other infection-related morbidity was not reduced significantly (adjusted OR 0.39, 95% CI 0.13–1.12) (Table 6). However, the effect size for endometritis was small; the rate was only 2.0% in the prophylaxis group and 2.6% in the no-prophylaxis group. Wound infections and other infection-related morbidity were even less common. Results were similar when patients with spontaneous rupture of the membranes (n=653) or with an unknown type of rupture (n=13) were excluded (Table 7). The analysis also was repeated limiting the patient population to the lowest risk group of patients (n=5,148). As such, patients with diabetes, heart disease, renal disease, connective tissue disease, and smoking were excluded, as were those who may have had emergency cesarean delivery, including cesarean for nonreassuring fetal heart tracing, bleeding previa, or abruption. In addition, patients with complications such as intraoperative transfusion or severe postpartum anemia (hemoglobin less than 8 g/dL), uterine or hypogastric artery ligation, bowel perforation, cystotomy, ureteral injury, broad ligament hematoma, uterine rupture, and cesarean hysterectomy were excluded. After adjusting for all the variables as listed in Table 6, with the exception of diabetes and smoking, the rate of endometritis was still significantly lower in the prophylaxis group (adjusted OR 0.29, 95% CI 0.17–0.51). However, the decreased rate of wound infection was no longer statistically significant (adjusted OR 0.81, 95% CI 0.34–1.97).
Based on this analysis, for every serious infection prevented, 113 women (95% CI 60–575) must receive antibiotic prophylaxis at the time of nonlaboring cesarean delivery. This may be an overestimation for populations that are at higher risk for postpartum infection-related complications than those delivering in Maternal–Fetal Medicine Unit hospitals, where the rates of postpartum endometritis and wound infection were low (2.2% and 0.7%, respectively).
We found that the use of perioperative antibiotics at the time of nonlaboring cesarean delivery significantly reduced the risks of postpartum endometritis and wound infection. It is well-established that both the presence and duration of labor and rupture of the membranes are associated with an increased risk of postpartum infection in women undergoing cesarean delivery.5 The current study appears to be the largest single study to evaluate the efficacy of perioperative antibiotics in the prevention of postpartum infection-related complications in women undergoing cesarean delivery before the onset of labor (8-10; Medline search 1950 through December 2008, key words “cesarean section,” “endometritis,” “antibiotic prophylaxis”; all languages). Because this was not a randomized trial, the antibiotic-treated group might be expected to be at a higher risk for infection-related complications given that, based on their risk profiles, their obstetric providers elected to administer prophylactic antibiotics. As a result, one would anticipate that any potential bias would lead to a higher rate of infection-related complications in the treated group, leading to a decrease in the treatment effect.
In a prospective observational study of 1,863 women in four community centers, Ehrenkrantz and colleagues report that endometritis or wound infection or both occurred in 3.7% of women undergoing nonlaboring cesarean delivery who did not receive antibiotic prophylaxis compared with 0.9% of those who did receive antibiotic prophylaxis (P<.01).8 However, in a randomized, double-blind, placebo-controlled trial, Bagratee and colleagues found no difference in rates of wound infection, endometritis, urinary tract infection, pneumonia, or febrile morbidity after antibiotic prophylaxis in 480 patients undergoing elective cesarean delivery.9 A meta-analysis of four studies by Chelmow and colleagues concludes that the risk of postpartum infection-related complications was reduced significantly by the use of perioperative antibiotics in patients undergoing cesarean delivery before labor and membrane rupture.10 The use of prophylactic antibiotics reduced the rate of postoperative fever (relative risk 0.25, 95% CI 0.14–0.44) and the risk of endometritis (relative risk 0.05, 95% CI 0.01–0.38). Only two studies report rates of wound infection, and the meta-analysis showed only a trend toward a reduction in wound infection (relative risk 0.59, 95% CI 0.24–1.45). Our study revealed a much more modest reduction in the risk of endometritis (adjusted OR 0.40, 95% CI 0.28–0.59), with a similar reduction in the rate of wound infection (adjusted OR 0.49, 95% CI 0.28–0.86). Our results are similar to those reported in the Cochrane Database of Systematic Reviews (OR 0.38, 95% CI 0.22–0.64 for endometritis and OR 0.7, 95% CI 0.53–0.99 for wound infections) after elective cesarean deliveries.5
Ehrenkranz and colleagues estimate that the use of antibiotic prophylaxis in low-risk women undergoing prelabor cesarean delivery could result in an annual national savings of approximately $9 million dollars.8 Using their own data, a cost–benefit analysis also was performed by Chelmow and colleagues. They used a relative risk of endometritis of 0.18 (95% CI 0.07–0.45) after antibiotic prophylaxis and a relative risk of fever of 0.47 (95% CI 0.32–0.66) in their calculations.11 Overall, administration of prophylactic antibiotics for elective cesarean delivery reduced costs by $30.66 per case (2% of the total cost). The authors concluded that “prophylactic antibiotic administration results in cost savings for elective cesarean delivery.”
Given the small effect size and the number of women who might be exposed to antibiotics to prevent a single case of endometritis, when choosing to administer prophylactic antibiotics in this clinical scenario, the practitioner also must consider the potential risks of antibiotic allergy, selection of resistant organisms, and the relative ease with which most postoperative infections are treated.
Owing to the limitations of our database, we are unable to address the important issue of whether prophylactic antibiotics should be administered before skin incision or after cord clamping. We are also unable to address the efficacy of the different types of antibiotics used. Our study does confirm, however, that the use of perioperative antibiotics at the time of cesarean delivery before labor, regardless of the presence of membrane rupture, significantly decreases the risks of endometritis and wound infection. Although there was also a reduction in other infection-related complications, this analysis did not reach statistical significance. However, the effect size is small, and a large number of women would need to be treated with antibiotics to prevent a single infection.
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