Clavulanic Acid, a Novel Inhibitor of β-Lactamases

Abstract

Clavulanic acid, Z-(2R,5R)-3-(β-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo-[3,2,0] heptane-2-carboxylic acid, has been shown to be an effective inhibitor of the β-lactamases of the Richmond types II, III, IV, and V. Inhibition is a time-dependent reaction and is irreversible. Clavulanic acid had poor antibacterial activity against Staphylococcus aureus, Enterobacteriaceae , and Pseudomonas aeruginosa , with minimal inhibitory levels greater than 25 μg/ml. It did inhibit the majority of Neisseria gonorrhoeae at 0.1 μg/ml and Haemophilus influenzae at 6.3 μg/ml. Clavulanic acid acted synergistically with penicillins and cephalosporins to inhibit β-lactamase-producing S. aureus and Enterobacteriaceae . Clavulanic acid combined with ampicillin inhibited β-lactamase-producing N. gonorrhoeae, H. influenzae, Escherichia coli, Salmonella typhi , and Shigella sonnei .