title: 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.
authors.affiliation: Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405.
authors.forename: Karen
authors.initials: K
authors.lastname: Bush
authors.affiliation: AstraZeneca Pharmaceuticals, Waltham, Massachusetts 02451.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bradford
mesh_terms: D015780:Carbapenems / Q000266:history / Q000494:pharmacology*; D002511:Cephalosporins / Q000266:history / Q000494:pharmacology*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008997:Monobactams / Q000266:history / Q000494:pharmacology*; D010406:Penicillins / Q000266:history / Q000494:pharmacology*; D018440:beta-Lactam Resistance / Q000187:drug effects; D065093:beta-Lactamase Inhibitors / Q000266:history / Q000494:pharmacology*
chemical_list: D015780:Carbapenems; D002511:Cephalosporins; D008997:Monobactams; D010406:Penicillins; D065093:beta-Lactamase Inhibitors