Induction of chromosomal β-lactamases by different concentrations of clavulanic acid in combination with ticardillin

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Abstract
The effect of different concentrations of clavulanic acid (CA) in combination with ticarcillin on β-lactamase production and ticarduin MIC was studied in four clinical isolates of Pseudomonas aeruginosa, Enterobacter cloacae, Serratla marcescens, Citrobacter freursdii and indole positive Proteus strains. Ticarcillin alone showed a low inducing effect for all species tested, Ser. marescens excepted. The increase in β-lactamase activity after addition of CA (2–10 mg/l) was strain and species dependent. No synergy or antagonism was observed on the ticarcillin MIC for the micro-organisms producing only a chromosomally mediated β-lactamase, though the susceptibility to ticarcillin strongly increased if the strains also produced a plasmid-mediated β-lactamase. Addition of 50 or 100 mg/l CA resulted in all strains, C. freundii excepted, in a strong increase in β-lactamase activity and in a strong synergistic effect on the ticarcillin MIC. However, these concentrations are unlikely to be achieved at clinical doses. Thus, irrespective of the inducing effect of ticarcillin and CA (2–10 mg/l) combinations, induction of the chromosomal β-lactamase did not result in a decrease in ticarcillin susceptibility.