Beta-Lactamase Inhibitors

Clavulanic acid, the first beta-lactamase inhibitor introduced into clinical medicine, was isolated from Streptomyces clavuligerus in the1970s. Clavulanate is a beta-lactamase inhibitor that is not effective by itself, but only when combined with penicillin-group antibiotics. Clavulanate can overcome antibiotic resistance in bacteria that secrete beta-lactamase, which otherwise inactivates most penicillins. When combined, e.g. with amoxicillin, clavulanate significantly lowered the amoxicillin MICs against S. aureus, K. pneumoniae, Proteus mirabilis, and E. coli. Beta-lactamase inhibitor compounds are effective against many susceptible organisms expressing class A beta-lactamases and are generally less effective against class B, C,and D beta-lactamases.

Biochemical mechanism: Clavulanic acid shares structural similarity with penicillin and is a classical irreversible ‘suicide inhibitor’; that can permanently inactivate the beta-lactamase through secondary chemical reactions in the enzyme active site.

Clavulanic acid

Literature: Drawz, SM & Bonomo, RA. Clinical Microbiology Reviews 2010, 23, 160–201

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