Affiliation:
1. Beecham Pharmaceuticals Research Division, Brockham Park, Betchworth, Surrey, RH3 7AJ, England
Abstract
A novel β-lactamase inhibitor has been isolated from
Streptomyces clavuligerus
ATCC 27064 and given the name clavulanic acid. Conditions for the cultivation of the organism and detection and isolation of clavulanic acid are described. This compound resembles the nucleus of a penicillin but differs in having no acylamino side chain, having oxygen instead of sulfur, and containing a β-hydroxyethylidine substituent in the oxazolidine ring. Clavulanic acid is a potent inhibitor of many β-lactamases, including those found in
Escherichia coli
(plasmid mediated),
Klebsiella aerogenes, Proteus mirabilis
, and
Staphylococcus aureus
, the inhibition being of a progressive type. The cephalosporinase type of β-lactamase found in
Pseudomonas aeruginosa
and
Enterobacter cloacae
P99 and the chromosomally mediated β-lactamase of
E. coli
are less well inhibited. The minimum inhibitory concentrations of ampicillin and cephaloridine against β-lactamase-producing, penicillin-resistant strains of
S. aureus, K. aerogenes, P. mirabilis
, and
E. coli
have been shown to be considerably reduced by the addition of low concentrations of clavulanic acid.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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