The effects of clavulanic acid and sulbactam on beta-lactamase biosynthesis.

Clavulanic acid and sulbactam were tested as inducers of beta-lactamase in 21 strains of Gram-negative bacteria. beta-Lactamase synthesis was inducible in all these strains, as demonstrated by the increased enzyme activities obtained when cells were grown in the presence of 10 mg/l of cefoxitin, the increase varying from 11- to 734-fold However, at the same concentration, neither inhibitor induced significant amounts of beta-lactamase, except in one strain of Providencia rettgeri, where both were potent inducers. When steps were taken to overcome the inhibitory effects of clavulanic acid and sulbactam, they were still found to be ineffective inducers. We conclude that, at therapeutic concentrations, clavulanic acid and sulbactam are generally poor inducers of beta-lactamase. Amoxycillin and ampicillin induced more beta-lactamase than the inhibitors, but were much less effective than cefoxitin, except for the strain of Prov. rettgeri.