Ertapenem for injection

Antibiotic approved for the prophylaxis of surgical site infection following elective colorectal surgery

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Ertapenem for injection
MERCKAntibiotic approved for the prophylaxis of surgical site infection following elective colorectal surgery

Ertapenem, a sterile, synthetic, parenteral, 1-beta methyl-carbapenem, is structurally related to beta-lactam antibiotics. This agent has demonstrated bactericidal activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria, caused by the inhibition of cell wall synthesis and mediated by ertapenem binding to penicillin-binding proteins. Ertapenem, previously approved for the treatment of a variety of moderate-to-severe bacterial infections, was approved by FDA on August 10, 2006, for the prophylaxis of surgical site infection following elective colorectal surgery in adults.

Efficacy. The efficacy of ertapenem for prophylaxis of surgical site infection following elective colorectal surgery in adults was evaluated in a multicenter, randomized, double-blind clinical trial comparing a single intravenous dose of ertapenem (1 g) with a single intravenous dose of cefotetan (2 g) administered over 30 minutes, 1 hour before surgery. Prophylaxis success was defined as no evidence of surgical site infection, postoperative anastomotic leak, or unexplained antibiotic use up to and including at the 4-week posttreatment follow-up visit. Prophylaxis success was measured in 2 patient subsets: the modified intent-to-treat (MITT) population, which included all patients who were randomized, were treated, and underwent elective colorectal surgery with adequate bowel preparation (ertapenem, n=451; cefotetan, n=450); and the clinically evaluable population, which included all patients from the MITT population who received a complete dose of study medication ≤2 hours before surgical incision and ≤6 hours before surgical closure (ertapenem, n=346; cefotetan, n=339); clinically evaluable patients also had no confounding factors that would interfere with the assessment of prophylaxis success. In the MITT population, the prophylaxis success rate 4 weeks after treatment was 58.3% for the ertapenem group and 48.9% for the cefotetan group (difference, 9.4%; 95% CI, 2.9%–15.9%; P=.002). Among clinically evaluable patients, the 4-week posttreatment prophylaxis success rate was 70.5% for the ertapenem group and 57.2% for the cefotetan group (difference, 13.3%; 95% CI, 6.1%–20.4%; P<.001). Prophylaxis failure due to surgical site infections among clinically evaluable patients occurred in 18.2% of the ertapenem group and 31.0% of the cefotetan group; postoperative anastomotic leak occurred in 2.9% of the ertapenem group and 4.1% of the cefotetan group, and unexplained antibiotic use occurred in 8.4% of the ertapenem group and 7.7% of the cefotetan group.

Dosing. The recommended dose of ertapenem for the prophylaxis of surgical site infection following elective colorectal surgery is 1 g administered as a single intravenous dose 1 hour before surgical incision. Before dose administration, a 1-g vial of ertapenem must be reconstituted with 10 mL of water for injection, 0.9% sodium chloride injection, or bacteriostatic water for injection. Contents must then be added to 50 mL of 0.9% sodium chloride, and infusion should be completed within 6 hours of reconstitution.