Clinical trials of extended spectrum penicillin/beta-lactamase inhibitors in the treatment of intra-abdominal infections. European and North American experience

Abstract

The clinical results with the beta-lactam/beta-lactamase inhibitor class of antimicrobials in the treatment of intra-abdominal infections are reviewed. The three agents now in clinical use--ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam--are effective against a broad variety of gram-positive and gram-negative organisms. The beta-lactamase inhibitor is an irreversible inactivator of beta-lactamase enzymes, which are produced by many gram-negative and gram-positive organisms. Randomized, prospective, clinical trials of each agent indicate clinical cure rates > 85% that are not significantly different from those obtained with second-generation cephalosporin or aminoglycoside plus antianaerobic comparators, with the exception of one study. Piperacillin/tazobactam has also been compared with imipenem, with equivalent or superior outcomes, depending on the dose of the imipenem comparator. Side effects in the non-penicillin-allergic patient are few. The incidence of abnormal renal function tests are generally lower than that obtained with aminoglycoside plus antianaerobic therapy. Introduction of this new beta-lactam antimicrobial group provides another important strategy for the adjunctive management of surgically treated, community-acquired, intra-abdominal infection.