The effects on ß-lactam susceptibility of phenotypic induction and genotypic derepression of ß-lactamase synthesis

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Abstract
We have compared the ability of ß-lactam antibiotics to induce ß-lactamase synthesis and antagonize the in-vitro activity of other ß-lactams and also to select mutants with derepressed ß-lactamase synthesis amongst representative Gramnegative bacilli that produce inducible ß-lactamases. Both imipenem and cefoxitin were potent inducers of ß-lactamase and were able to antagonize the activity of other ß-lactams against isolates of Enterobacter cloacae, Citrobacter freundii and Pseudomonas aeruginosa when the two ß-lactams were present simultaneously. However, there was no antagonism for any compound against any of the organisms when the imipenem or cefoxitin was removed immediately before susceptibility to the other compounds was measured.Cefotaxime was a less potent inducer of ß-lactamase and failed to antagonize the activity of other compounds, even when present concurrently with them. Neither imipenem nor cefoxitin induced ß-lactamase synthesis in a strain of Escherichia coli, nor did they antagonize the activity of other ß-lactams against this strain. Imipenem was compared with cefotaxime and cefoxitin as an agent for the selection of ß-lactam-resistant variants. Resistant variants were obtained from isolates of Ent. cloacae, C. freundii and p. aeruginosa when cefotaxime or cefoxitin was used as the selective agent. Most of them synthesized ß-lactamase constitutively and showed reduced susceptibility to a wide range of ß-lactams, but not to imipenem. Variants with reduced susceptibility to imipenem were obtained only from the two isolates of P. aeruginosa. They did not show cross resistance to other ß-lactams and were not distinguishable from the parent strains in ß-lactamase production.

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