Addition of postoperative cephalexin plus metronidazole to preoperative cefazolin reduces surgical site infection in women with obesity having cesarean delivery

EBM Focus - Volume 12, Issue 39

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Reference: JAMA 2017 Sep 19;318(11):1026 (level 1 [likely reliable] evidence)

  • Obesity is associated with increased risk of surgical site infection (SSI) following cesarean delivery.
  • The efficacy of adjunct postoperative antimicrobial prophylaxis to prevent SSI was investigated in a single-center trial with 403 women (mean age 28 years) with pre-pregnancy BMI ≥ 30 kg/m2 having cesarean delivery and receiving preoperative cefazolin 2 g IV randomized to cephalexin 500 mg plus metronidazole 500 mg vs. placebo orally every 8 hours for 48 hours after cesarean delivery.
  • Women receiving adjunct postoperative antimicrobial prophylaxis had significantly lower rates of SSI (in 6.4% vs. 15.4% with placebo, p = 0.01, NNT 12), but cephalexin and metronidazole are both excreted in breast milk and their benefits in preventing SSI should be weighed against potential harms associated with disruption of early breastfeeding.

Antimicrobial prophylaxis prior to skin incision is recommended for women having cesarean delivery (WHO 2015, RCOG 2015, BMJ 2011, Obstet Gynecol 2010). In women treated with antibiotic prophylaxis, an increased risk of surgical site infection (SSI) following cesarean delivery has been shown to be associated with increasing maternal body mass index (BMI) (Obstet Gynecol 2014, BJOG 2012). A single-center randomized trial was conducted to investigate the efficacy of adjunct postoperative antimicrobial prophylaxis to reduce SSI in women with obesity having cesarean delivery. In this trial, 403 women (mean age 28 years) with pre-pregnancy BMI ≥ 30 kg/m2 receiving preoperative cefazolin 2 g IV were randomized to cephalexin 500 mg plus metronidazole 500 mg vs. placebo orally every 8 hours for 48 hours starting 8 hours after the preoperative cefazolin IV dose. At randomization, women were stratified by membrane status before delivery. Preoperative skin preparation was performed with chlorhexidine or with povidone-iodine if the woman was allergic to chlorhexidine. The surgical procedure was performed using a Pfannenstiel incision in 95% of the women and sutures were used to close the skin in 95%. SSI was defined as a superficial- or deep-incisional infection or infection of an organ or space within 30 days after delivery.

Women receiving postoperative antimicrobial prophylaxis had significantly lower rates of SSI (in 6.4% vs. 15.4% with placebo, p = 0.01, NNT 12) and cellulitis (in 5.9% vs. 13.4% with placebo, p = 0.04, NNT 14), and a statistically nonsignificant lower rate of endometritis (in 1% vs. 4% with placebo, p = 0.05). There were no significant differences in rates of any defect in incisional integrity, fever of unknown etiology, or wound separation. In addition, no serious adverse events were observed. In post hoc subgroup analyses based on pre-delivery membrane status, the reduced risk of SSI with adjunct postoperative antimicrobial prophylaxis was statistically significant in 118 women with ruptured membranes (in 9.5% vs. 30.2% with placebo, p = 0.008, NNT 5), but not in 264 women with intact membranes (5% vs. 8.7% with placebo).

This trial demonstrated that for women with pre-pregnancy BMI ≥ 30 kg/m2 having cesarean delivery and pre-operative cefazolin 2 g IV, the addition of a postoperative 48-hour course of cephalexin 500 mg plus metronidazole 500 mg orally reduces the risk of SSI and cellulitis. Post hoc analyses suggest that the benefit of postoperative prophylaxis may be limited to women with rupture of membranes before cesarean delivery. However, additional research is needed to confirm this supposition, particularly as the majority of women in the subgroup with intact membranes did not have contractions leading to cervical change before cesarean delivery was performed. It should be noted that cephalexin and metronidazole are excreted into breastmilk and caution is recommended before using cephalexin in breastfeeding mothers (FDA DailyMed 2007 Mar 9) and breastfeeding mothers taking metronidazole should be instructed to discard their milk for the duration of therapy and for 24 hours after therapy ends (FDA DailyMed 2016 Jun 8). In summary, the benefit of adjunct postoperative antimicrobial prophylaxis to prevent SSI should be weighed against the potential harms associated with disruption of early breastfeeding in women with obesity having cesarean delivery. Further studies defining the population of women with obesity who would most benefit from adjunct postoperative antimicrobial prophylaxis may help limit unnecessary antibiotic exposure.

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