Ertapenem is one of the carbapenems and is characterized by a high protein-binding percentage and a long half-life which permits once-daily administration (1 gm IV or IM q24h). It was licensed in the US in 2001, and currently has FDA indications for use in (1) complicated intra-abdominal infections, (2) complicated skin and skin-structure infections (including diabetic foot infections without osteomyelitis), (3) acute pelvic infection (postpartum endomyometritis, septic abortion, and post surgical gynecologic infections), (4) complicated urinary tract infections, and (5) community-acquired pneumonia. It is also FDA indicated in pediatrics (>=3 months of age) for the above indications. In addition, its use in the prophylaxis of surgical-site infection following elective colorectoal surgery was also approved by FDA in 2006.
Ertapenem has a broad-spectrum antibacterial activity against many Gram-negative and Gram-positive bacteria, and several anaerobic organisms. With the exception of metallo-beta-lactamase, it has high stability against nearly all beta-lactamases, including ESBLs and AmpC. However, it is not active against Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia, Burkholderia cepacia, and Aeromonas spp., entorococci, MRSA, penicillin-resistant Streptococcus pneumoniae, Clostridium difficile and Lactobacillus spp.
Ertapenem does not interact with cytochrom p450 or P-glycoprotein. The risk of seizure is reported at 0.5% in clinical trials.
Complicated intra-abdominal infections
Ertapenem was compared with piperacillin/tazobactam as therapy following adequate surgical management of complicated intra-abdominal infections in a prospective, randomized, controlled, double-blind Phase III trial. The clinical (79.3% vs. 76.2%) and microbiological cure rate (86.7% vs. 81.2%) was similar in ertapenem and piperacillin/tazobactam groups. However, ertapenem had higher efficacy rates than piperacillin/tazobactam did in patients with non-appendiceal infection (83.8% vs. 68.8%), generalized peritonitis (83.3% vs. 73.6%), and postoperative infection (75.0% vs. 40.9%).
Complicated urinary tract infections
Ertapenem was compared with ceftriaxon in two prospective, randomized, double-blind, multicenter trials for patients with complicated urinary tract infections including pyelonephritis; the favorable microbiological responses between the two treatment groups were similar in the two studies (91.8% vs. 93.0% and 85.6% vs. 84.9%, respectively).
Complicated Skin and Skin Structure Infections
Ertapenem was compared with piperacillin/tazobactam for complicated skin and skin-structure infections in a prospective, randomized, double-blind trial; the success rates for the two groups were equivalent (83.9% in 168 patients vs. 85.3% in 170 patients).
Diabetic foot infections without osteomyelitis
Ertapenem was compared with piperacillin/tazobactam for adult diabetes patients with foot infection and without osteomyelitis in a randomized, double-blind multi-center clinical efficacy trial (the SIDESTEP study); rates of favorable clinical response (75% in 204 patients vs. 70.8% in 202 patients), microbiological outcomes, and adverse events were similar between the two groups.
Acute pelvic infections
Ertapenem was compared with piperacillin/tazobactam for acute pelvic infections in a multi-center double-blind study; the cure rates (93.9% in 163 patients vs. 91.5% in 153 patients) and the frequency and severity of drug-related adverse events were similar in both groups at 2-4 weeks post-therapy.
