The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam
- PMID:27327972
- DOI: 10.4155/fmc-2016-0078
The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam
Abstract
Avibactam, which is the first non-β-lactam β-lactamase inhibitor to be introduced for clinical use, is a broad-spectrum serine β-lactamase inhibitor with activity against class A, class C, and, some, class D β-lactamases. We provide an overview of efforts, which extend to the period soon after the discovery of the penicillins, to develop clinically useful non-β-lactam compounds as antibacterials, and, subsequently, penicillin-binding protein and β-lactamase inhibitors. Like the β-lactam inhibitors, avibactam works via a mechanism involving covalent modification of a catalytically important nucleophilic serine residue. However, unlike the β-lactam inhibitors, avibactam reacts reversibly with its β-lactamase targets. We discuss chemical factors that may account for the apparently special nature of β-lactams and related compounds as antibacterials and β-lactamase inhibitors, including with respect to resistance. Avenues for future research including non-β-lactam antibacterials acting similarly to β-lactams are discussed.
Keywords: DBO; antibiotic resistance; avibactam; diazabicyclo[3.2.1]octane; lactivicin; metallo-β-lactamase; penicillin-binding protein; serine β-lactamase; β-lactam; β-lactamase inhibitor; γ-lactam.
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