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Issue 9, 2018
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β-lactam/β-lactamase inhibitor combinations: an update

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Abstract

Antibiotic resistance caused by β-lactamase production continues to present a growing challenge to the efficacy of β-lactams and their role as the most important class of clinically used antibiotics. In response to this threat however, only a handful of β-lactamase inhibitors have been introduced to the market over the past thirty years. The first-generation β-lactamase inhibitors (clavulanic acid, sulbactam and tazobactam) are all β-lactam derivatives and work primarily by inactivating class A and some class C serine β-lactamases. The newer generations of β-lactamase inhibitors including avibactam and vaborbactam are based on non-β-lactam structures and their spectrum of inhibition is extended to KPC as an important class A carbapenemase. Despite these advances several class D and virtually all important class B β-lactamases are resistant to existing inhibitors. The present review provides an overview of recent FDA-approved β-lactam/β-lactamase inhibitor combinations as well as an update on research efforts aimed at the discovery and development of novel β-lactamase inhibitors.

Graphical abstract: β-lactam/β-lactamase inhibitor combinations: an update

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Article information


Submitted
08 Jul 2018
Accepted
16 Aug 2018
First published
17 Aug 2018

Med. Chem. Commun., 2018,9, 1439-1456
Article type
Review Article

β-lactam/β-lactamase inhibitor combinations: an update

K. H. M. E. Tehrani and N. I. Martin, Med. Chem. Commun., 2018, 9, 1439
DOI: 10.1039/C8MD00342D

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