Ertapenem versus cefotetan prophylaxis in elective colorectal surgery

N Engl J Med. 2006 Dec 21;355(25):2640-51. doi: 10.1056/NEJMoa054408.

Abstract

Background: Ertapenem, a long-acting carbapenem, may be an alternative to the recommended prophylactic antibiotic cefotetan.

Methods: In this randomized, double-blind trial, we assessed the efficacy and safety of antibiotic prophylaxis with ertapenem, as compared with cefotetan, in patients undergoing elective colorectal surgery. A successful outcome was defined as the absence of surgical-site infection, anastomotic leakage, or antibiotic use 4 weeks postoperatively. All adverse events were collected until 14 days after the administration of antibiotic prophylaxis.

Results: Of the 1002 patients randomly assigned to study groups, 901 (451 in the ertapenem group and 450 in the cefotetan group) qualified for the modified intention-to-treat analysis, and 672 (338 in the ertapenem group and 334 in the cefotetan group) were included in the per-protocol analysis. After adjustment for strata, in the modified intention-to-treat analysis, the rate of overall prophylactic failure was 40.2% in the ertapenem group and 50.9% in the cefotetan group (absolute difference, -10.7%; 95% confidence interval [CI], -17.1 to -4.2); in the per-protocol analysis, the failure rate was 28.0% in the ertapenem group and 42.8% in the cefotetan group (absolute difference, -14.8%; 95% CI, -21.9 to -7.5). Both analyses fulfilled statistical criteria for the superiority of ertapenem. In the modified intention-to-treat analysis, the most common reason for failure of prophylaxis in both groups was surgical-site infection: 17.1% in the ertapenem group and 26.2% in the cefotetan group (absolute difference, -9.1; 95% CI, -14.4 to -3.7). In the treated population, the overall incidence of Clostridium difficile infection was 1.7% in the ertapenem group and 0.6% in the cefotetan group (P=0.22).

Conclusions: Ertapenem is more effective than cefotetan in the prevention of surgical-site infection in patients undergoing elective colorectal surgery but may be associated with an increase in C. difficile infection. (ClinicalTrials.gov number, NCT00090272 [ClinicalTrials.gov].).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Antibiotic Prophylaxis*
  • Cefotetan / administration & dosage
  • Cefotetan / adverse effects
  • Cefotetan / therapeutic use*
  • Clostridioides difficile
  • Clostridium Infections
  • Colorectal Surgery*
  • Double-Blind Method
  • Elective Surgical Procedures
  • Ertapenem
  • Female
  • Humans
  • Infusions, Intravenous
  • Logistic Models
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Surgical Wound Infection / prevention & control*
  • Treatment Failure
  • beta-Lactams / administration & dosage
  • beta-Lactams / adverse effects
  • beta-Lactams / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Cefotetan
  • Ertapenem

Associated data

  • ClinicalTrials.gov/NCT00090272