Postoperative Antibiotics After Cesarean Delivery to Reduce SSI
September 1, 2025
By Alexandra Morell, MD
Synopsis: This randomized, double-blind clinical trial including 321 women with a pre-pregnancy body mass index > 30 kg/m2 demonstrated no difference in surgical site infection composite between participants receiving oral cephalexin and metronidazole for 48 hours after cesarean delivery compared to placebo (5.6% vs. 6.8%; odds ratio, 0.80; 95% confidence interval, 0.33-2.22; P = 0.64).
Source: Saad AF, Goldman B, Spencer N, et al. Prophylactic oral cephalexin and metronidazole compared with placebo after cesarean delivery to reduce infection complications in women with obesity: A randomized controlled trial. Obstet Gynecol. 2025;146(1):113-120.
Cesarean delivery is an established risk factor for postpartum morbidity, including puerperal infection.1 The risk of surgical site infections (SSIs) after cesarean delivery in obese patients is approximately 12% to 20%, compared to 0.06% to 10% in non-obese patients.2 Other than obesity, risk factors associated with SSI include alcohol use disorder, post-term pregnancy, very early preterm pregnancy, chorioamnionitis, premature rupture of membranes within 24 hours, iron deficiency anemia, failed trial of labor, prolonged operative time, prior hysterotomy (not from cesarean delivery), tobacco use disorder, hypertensive disorders of pregnancy, single marital status, unemployment, and having a surgeon from a non-obstetrics specialty.3
This was a randomized, double-blind clinical trial that aimed to determine if the use of prophylactic antibiotics after cesarean delivery could reduce SSIs in obese patients with membrane rupture prior to surgery. It was conducted at two medical centers in Texas over a six-year period. Inclusion criteria included women older than 18 years of age with a pre-pregnancy body mass index (BMI) > 30 kg/m2 undergoing cesarean delivery with ruptured membranes for at least four hours. Exclusion criteria included immunosuppressive conditions such as human immunodeficiency virus (HIV), use of immunosuppressant medications, use of steroids other than for fetal lung maturity, fetal death, clinical comorbidities, allergies to standard antibiotic regimens, or conditions where postoperative antibiotics were indicated.
All participants received standard preoperative prophylactic antibiotics, including intravenous cefazolin and azithromycin within one hour of skin incision. Cesarean deliveries were performed in a standard fashion with preference for Pfannenstiel incision, closure of the fascia with a monofilament suture, closure of the subcutaneous tissue if more than 2 cm deep, and subcuticular closure of the skin with either polyglactin or poliglecaprone suture. Participants then were randomized in a 1:1 fashion to receive 500 mg oral cephalexin and 500 mg oral metronidazole or placebo antibiotic every eight hours for 48 hours after delivery.
The primary outcome was an infection composite, including endometritis, SSI, and post-cesarean infections, such as pelvic septic thrombophlebitis and pelvic or abdominal abscesses, 30 days following surgery. Secondary outcomes included wound cellulitis, wound hematoma or seroma, wound separation, puerperal fever, emergency department wound evaluation, obstetric triage wound evaluation, and postpartum wound readmission. Postoperative evaluations were conducted at two and six weeks postpartum.
Power calculations determined that a total of 302 participants were necessary to detect a 50% reduction in SSI (from 25% in the placebo group to 12.5% in the antibiotic group). A total of 1,281 patients were screened with enrollment of 321 patients (160 in the antibiotic group and 161 in the placebo group). The mean BMI was 38.4 kg/m2 and the mean age was 27.5 years. Eighty-four percent of patients identified as white and 63% identified as Hispanic or Latina. The most common indications for cesarean delivery in the cohort were labor arrest and nonreassuring fetal status. There were no statistically significant differences between the antibiotic and placebo groups regarding demographic variables, indication for cesarean delivery, duration of surgery, type of skin closure, or length of hospital stay.
In the intention-to-treat population, the primary outcome (SSI composite) occurred in 5.6% of the antibiotic group (n = 9 out of 160) and 6.8% of the placebo group (n = 11 out of 161), reflecting an odds ratio (OR) of 0.81 (95% confidence interval [CI], 0.33 to 2.02). For the secondary outcomes, the rates of fever (7.4% antibiotic vs. 5.7%), endometritis (2.0% antibiotic vs. 1.9%), wound separation (4.0% antibiotic vs. 5.1%), wound seroma (2.7% antibiotic vs. 1.3%), wound cellulitis (2.6% antibiotic vs. 2.6%), emergency department wound evaluation (2.0% antibiotic vs. 3.2%), and obstetric triage wound evaluation (4.0% antibiotic vs. 5.8%) were not statistically significant between the two groups.
There were two postpartum readmissions (1.3%) in the antibiotic group and three readmissions (1.9%) in the placebo group (OR, 0.70; 95% CI, 0.12 to 2.24). Of the 321 randomized participants, 88.5% (n = 284) completed the study protocol. Analysis of only the participants who completed study protocol also demonstrated no difference in the primary SSI composite outcome or any of the secondary outcomes between the two groups.
Commentary
The American College of Obstetricians and Gynecologists (ACOG) currently recommends 2 g of intravenous cefazolin within one hour of surgery for antibiotic prophylaxis at the time of cesarean delivery.4 An increased dose of 3 g is recommended for patients with a weight more than 120 kg. For patients with a serious allergy (including anaphylaxis, angioedema, respiratory distress, or urticaria) to cephalosporins, clindamycin combined with an aminoglycoside antibiotic such as gentamicin is the treatment of choice. In addition, 500 mg of intravenous azithromycin can be added for women undergoing nonelective cesarean deliveries. Preventive antibiotics should be re-dosed for long procedures (if the surgery is longer than two drug half-lives of the antibiotic or four hours for cefazolin) or for blood loss greater than 1,500 mL during the procedure.
Given the success of preoperative antibiotics in reducing SSI, investigation of postoperative antibiotic prophylaxis, especially in obese patients who have a higher risk of SSI, makes sense. This study by Saad and colleagues demonstrated that the use of postoperative oral antibiotics in obese individuals did not significantly affect the incidence of SSI after cesarean delivery. This contrasts with one prior study investigating post-cesarean antibiotic prophylaxis, which found a lower rate of SSI (6.4% vs. 15.4%; risk ratio, 0.41; 95% CI, 0.22 to 0.77) when receiving oral cephalexin and metronidazole for 48 hours after delivery.5 However, this study was performed before the addition of intravenous azithromycin preoperatively in patients with ruptured membranes; thus, this potentially could account for the difference between studies.
In addition to antibiotics, the routine use of alcohol-based skin preparation prior to cesarean delivery also is recommended.4 Consideration of a vaginal preparation in laboring patients or those with ruptured membranes with povidone-iodine or chlorhexidine gluconate also is part of ACOG guidelines.4 Intraoperative closure of the subcutaneous tissue if ≥ 2 cm thick may reduce wound complications.6 Lastly, the use of evidence-based surgical bundles is associated with a reduced risk of SSI after cesarean delivery.7
Preoperative skin preparation and antibiotic administration are extremely important in the prevention of SSI. Providers should continue to focus on the recommended and established techniques for reduction of SSI outlined by ACOG. In addition, providers can consider implementing a perioperative surgical bundle at their institution, if not already implemented, as a potential method for SSI reduction.
Alexandra Morell, MD, is Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY.
References
1. Deneux-Tharaux C, Carmona E, Bouvier-Colle MH, Br art G. Postpartum maternal mortality and cesarean delivery. Obstet Gynecol. 2006;108(3, Part 1):541-548.
2. Ekanem E, Ngene NC, Moodley J, Konje J. Prevention of surgical site infection and sepsis in pregnant obese women. Best Pract Res Clin Obstet Gynaecol. 2023;91:102406.
3. Jang SR, Chen BPH, Guilfoyle J, et al. Surgical site infection following cesarean delivery incidence, risk factors, and association with incremental healthcare use. AJOG Glob Rep. 2022;3(1):100144.
4. Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin No. 199: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2018;132(3):e103-e119. [Erratum in: Obstet Gynecol. 2019;134(4):883-884.]
5. Valent AM, DeArmond C, Houston JM, et al. Effect of post-cesarean delivery oral cephalexin and metronidazole on surgical site infection among obese women: A randomized clinical trial. JAMA. 2017;318(11):1026-1034. [Erratum in: JAMA. 2017;318(18):1832.]
6. Dahlke JD, Mendez-Figueroa H, Rouse DJ, et al. Evidence-based surgery for cesarean delivery: An updated systematic review. Am J Obstet Gynecol. 2013;209(4):294-306.
7. Carter EB, Temming LA, Fowler S, et al. Evidence-based bundles and cesarean delivery surgical site infections: A systematic review and meta-analysis. Obstet Gynecol. 2017;130(4):735-746.