Ertapenem: a Group 1 carbapenem with distinct antibacterial and pharmacological properties

Abstract

Ertapenem, a Group 1 carbapenem, is the most recent beta-lactam antibiotic to enter clinical practice in the USA and Europe. While structurally a carbapenem, the overall molecular structure of ertapenem has been modified to focus its antibacterial spectrum on important community-acquired aerobic and anaerobic pathogens, and to increase its plasma half-life, permitting once-a-day dosing for this parenteral antibiotic. A number of chemical features are responsible for the unique properties of ertapenem. The inclusion of a trans-1-hydroxyethyl group in the structure of ertapenem enables the drug to maintain antibacterial efficacy against the vast majority of beta-lactamase-producing organisms. A critical 1beta-methyl substituent shields the beta-lactam carbonyl group and serves to reduce dehydropeptidase (DHP)-1 catalysed hydrolysis of the beta-lactam, enabling ertapenem to be administered without a DHP-1 inhibitor. A meta-substituted benzoic acid substituent increases the molecular weight and lipophilicity of the molecule, and the carboxylic acid moiety, ionized at physiological pH, results in ertapenem having a net negative charge. As a result, ertapenem is highly protein bound and has an extended half-life, permitting a once-a-day treatment regimen.