Induction of chromosomal beta-lactamases by different concentrations of clavulanic acid in combination with ticarcillin.

Abstract

The effect of different concentrations of clavulanic acid (CA) in combination with ticarcillin on beta-lactamase production and ticarcillin MIC was studied in four clinical isolates of Pseudomonas aeruginosa, Enterobacter cloacae, Serratia marcescens, Citrobacter freundii and indole positive Proteus strains. Ticarcillin alone showed a low inducing effect for all species tested, Ser. marcescens excepted. The increase in beta-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 beta-lactamase, though the susceptibility to ticarcillin strongly increased if the strains also produced a plasmid-mediated beta-lactamase. Addition of 50 or 100 mg/l CA resulted in all strains. C. freundii excepted, in a strong increase in beta-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 beta-lactamase did not result in a decrease in ticarcillin susceptibility.