Induction of chromosomal beta-lactamases by different concentrations of clavulanic acid in combination with ticarcillin.
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.
D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D002876:Chromosomes, Bacterial / Q000187:drug effects; D002954:Citrobacter / Q000187:drug effects / Q000201:enzymology; D002969:Clavulanic Acids / Q000494:pharmacology*; D004338:Drug Combinations; D004754:Enterobacter / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology*; D011511:Proteus / Q000187:drug effects / Q000201:enzymology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D012706:Serratia marcescens / Q000187:drug effects / Q000201:enzymology; D013982:Ticarcillin / Q000494:pharmacology*; D001618:beta-Lactamases / Q000096:biosynthesis*
D002969:Clavulanic Acids; D004338:Drug Combinations; D010406:Penicillins; D001618:beta-Lactamases; D013982:Ticarcillin