Resistance to beta-lactams--the permutations.

Abstract

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.

• Authors: S G B Amyes
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 15 Issue 6 Pg. 525-35 (Dec 2003) ISSN: 1120-009X [Print] England
• PMID: 14998075 (Publication Type: Comparative Study, Journal Article, Review)

Chemical References

• beta-Lactams

Topics

• Biological Availability
• Community-Acquired Infections (drug therapy, microbiology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Resistance, Multiple, Bacterial
• Humans
• Microbial Sensitivity Tests
• Sensitivity and Specificity
• beta-Lactam Resistance
• beta-Lactams (pharmacokinetics, therapeutic use)