Chicago - Ertapenem (Invanz), a new once-a-day parenteral beta-lactam antimicrobial agent, has been shown to be effective, safe, and well tolerated for the treatment of complicated skin and skin structure infections, providing a broad spectrum of antibacterial activity, Donald Graham, M.D., said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Ertapenem is a novel alternative for complicated skin and skin structure infections commonly caused by more than one microorganism," said Dr. Graham, chairman, department of infectious diseases, Springfield Clinic, Springfield, Ill. "It has the convenience of a once-a-day administration, is equivalent to comparators, using either intramuscular or intravenous methods of administration, and, thus, gives physicians a new class of drugs to combat these infections, which are frequently caused by a mixture of Gram-positive and Gram-negative aerobic and anaerobic bacteria."

Infectious processes

Complicated bacterial infections of the skin and associated structures are common and include a variety of infectious processes such as lower extremity infections in patients with diabetes mellitus, perineal cellulitis or abscesses, and other spontaneous, traumatic, deep, and superficial soft tissue infections, Dr. Graham explained.

These community-acquired, mixed infections are commonly caused by a combination of Gram-positive and Gram-negative aerobic and anaerobic bacteria. Ertapenem has been shown to be effective against staphylococci and streptococci, most pathogenic anaerobes, and members of the Enterobacteriaceae (including strains producing extended spectrum beta-lactamases). The minimum inhibitory concentration for 90 percent of organisms (MIC90) of this structurally unique carbapenem is well below the proposed provisional susceptibility breakpoint of the compound (4 mg/ml). The new antibiotic has minimal activity, however, against enterococci and nonfermentative Gram-negative bacilli, including Pseudomonas species and is not effective against methicillin-resistant Staphylococcus aureus. Based on its spectrum of activity and its long half-life, ertapenem is being investigated as a once-a-day parenteral beta-lactam antimicrobial with the potential of being used as monotherapy for the treatment of community-acquired, mixed infections.

A prospective, randomized, comparative equivalence, multicenter trial was carried out at 33 centers in the United States and 11 centers in Central and South America to assess the safety and efficacy of ertapenem compared to piperacillin/tazobactam, Dr. Graham said. A total of 540 patients with CSSSI were randomized to ertapenem 1.0 g once daily IV (274 pts) or piperacillin/tazobactam 3.375 g IV dosed every six hours (266 pts).

The clinically evaluable population included 66.5 percent (359) of the randomized patients, with 185 in the ertapenem group and 174 in the piperacillin/tazobactam group, Dr. Graham continued. Of these patients, 85.2 percent (306) were micrologically evaluable (83.8 percent, 155, of the ertapenem group and 86.8 percent, 151, of the piperacillin/tazobactam group). The primary efficacy outcome determination was the proportion of clinically evaluable patients with a favorable clinical response assessment at the test of cure evaluation (days 10 to 21 posttreatment). The secondary efficacy outcome determination was the proportion of microbiologically evaluable patients with both a favorable clinical and microbiological response at the end of treatment visit (seven to 14 days) and test-of-cure (10 to 20 days posttreatment).

In this study, Dr. Graham noted, ertapenem was as effective as piperacillin/tazobactam for the treatment of CSSSI, with a clinical response in clinically evaluable patients of 82.4 percent in the ertapenem group and 84.4 percent in the piperacillin/tazobactam group, at test-of-cure. In the microbiologically evaluable group, the combined clinical and microbiological response was 81.9 percent for recipients of ertapenem and 82.1 percent for those who received piperacillin/tazobactam.

Diabetic patient analysis

An additional efficacy analysis was carried out in diabetic patients with lower extremity infections, Dr. Graham said. In 66 clinically evaluable diabetic patients, of whom 35 received ertapenem and 31 received piperacillin/tazobactam, the clinical response at test-of-cure was 65.7 percent in the ertapenem group and 71 percent in the piperacillin/tazobactam group, with combined clinical and microbiological responses of 63 percent (17 of 27) for ertapenem and 64.3 percent (18 of 28) for piperacillin/tazobactam.

Overall, Dr. Graham pointed out, ertapenem was generally well tolerated and its safety profile was similar to that of piperacillin/tazobactam. The most commonly reported drug-related clinical adverse events in both groups were infused vein complications (6.3 percent on ertapenem and 5.4 percent on piperacillin/tazobactam) and diarrhea (5.5 percent ertapenem and 8.9 percent on piperacillin/tazobactam). Nausea, pruritus, and rash also were reported in both treatment groups, at levels less than 3 percent.