Resistance to β-Lactams - The Permutations

Abstract

The β-lactam family of antimicrobials, in particular penicillins and cephalosporins, is the mainstay of treatment for community-acquired infections. However, the emergence of resistant isolates to these agents has raised concerns regarding the continued efficacy of existing therapies. Resistance to β-lactams is most commonly expressed by the microbial production of β-lactamases that hydrolyze the β-lactam ring. Three further resistance mechanisms include conformational changes in penicillin-binding proteins (PBPs); permeability changes in the outer membrane; and active efflux of the antimicrobial. In addition to the pre-requisite efficacy and tolerability profiles, new β-lactams should address these four resistance mechanisms. Overcoming resistance may be a serendipitous event or arrived at by design. A unique synthetic β-lactam class, which demonstrates promise in terms of its activity against the range of bacteria responsible for communityacquired infections and its inherent stability to hydrolysis by β-lactamases, is the penems. This discrete class of hybrid molecules combines properties from the penicillin (penam) and cephalosporin (cephem) β-lactam classes. Faropenem is an example of a penem with a broad spectrum of activity designed to address these resistance issues.