β-Lactams and β-Lactamase Inhibitors: An Overview

Abstract

β-Lactams are the most widely used class of antibiotics. Since the discovery of benzylpenicillin in the 1920s, thousands of new penicillin derivatives and related β-lactam classes of cephalosporins, cephamycins, monobactams, and carbapenems have been discovered. Each new class of β-lactam has been developed either to increase the spectrum of activity to include additional bacterial species or to address specific resistance mechanisms that have arisen in the targeted bacterial population. Resistance to β-lactams is primarily because of bacterially produced β-lactamase enzymes that hydrolyze the β-lactam ring, thereby inactivating the drug. The newest effort to circumvent resistance is the development of novel broad-spectrum β-lactamase inhibitors that work against many problematic β-lactamases, including cephalosporinases and serine-based carbapenemases, which severely limit therapeutic options. This work provides a comprehensive overview of β-lactam antibiotics that are currently in use, as well as a look ahead to several new compounds that are in the development pipeline.

Figure 1.

Proportion of prescriptions in the United States for injectable antibiotics by class for years 2004–2014. The percentage of standard units for each injectable antibiotic prescribed in the United States from 2004 to 2014 is shown as follows: β-lactams, 65.24%; glycopeptides, 9%; fluoroquinolones, 8%; macrolides/ketolides, 6%; aminoglycosides, 5%; polymyxins, 1%; trimethoprim/sulfamethoxazole, 0.5%; tetracyclines (excluding tigecycline), 0.4%; all other antibiotics (including daptomycin, linezolid, and tigecycline), 4.21%. (Data from the IMS MDART Quarterly Database on file at AstraZeneca.)