Resistance to beta-lactams--the permutations.
The beta-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 beta-lactams is most commonly expressed by the microbial production of beta-lactamases that hydrolyze the beta-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 beta-lactams should address these four resistance mechanisms. Overcoming resistance may be a serendipitous event or arrived at by design. A unique synthetic beta-lactam class, which demonstrates promise in terms of its activity against the range of bacteria responsible for community-acquired infections and its inherent stability to hydrolysis by beta-lactamases, is the penems. This discrete class of hybrid molecules combines properties from the penicillin (penam) and cephalosporin (cephem) beta-lactam classes. Faropenem is an example of a penem with a broad spectrum of activity designed to address these resistance issues.
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Medical Microbiology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, UK.
D001682:Biological Availability; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D012680:Sensitivity and Specificity; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D047090:beta-Lactams