The ability of β-lactam antibioties to select mutants with derepressed β-lactamase synthesis from Citrobacter freundii

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Abstract
The ability of β-lactam compounds to induce synthesis of the class C β-lactamase of Citrobacter freundii was assessed both directly and indirectly, the latter by measurement of the different susceptibilities of strains with inducible and derepressed β-lactamase synthesis and those of a β-lactamase-negative strain. Most β-lactam compounds were poor inducers but ampicillin, amoxycillin and cephalexin were moderately good inducers and cefoxitin, imipenem and meropenem were strong inducers. The ability of the compounds to select mutants in which the synthesis of the β-lactamase was derepressed was also assessed. Imipenem and temocillin, which had a high degree of stability to the β-lactamase failed to select such mutants or were very poor selectors. In contrast, most other compounds showed considerable lability to the β-lactamase and readily selected derepressed mutants, whether they were strong inducers of β-lactamase synthesis (for example cefoxitin) or poor inducers (cefotaxime, ceftazidime and many other compounds). Thus it appears that lability to the β-lactamase is a more important factor in determining whether or not a compound will select derepressed mutants than the power of the compound as an inducer of β-lactamase synthesis, since induction results in the production of less β-lactamase than derepression as a result of mutation.

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