1887

Abstract

Summary.

The activities of -lactam antibiotics were compared against clinical isolates and mutants which had inducible, stably-derepressed, and basal expression of a I 8·4 subtype of the Ia chromosomal -lactamase. These activities were correlated with the results of studies of the -lactamase-lability and -lactamase-inducer-power of the antibiotics. Cefoxitin and ampicillin were labile, and induced -lactamase production strongly at concentrations below their MIC values. Consequently, -lactamase-inducible and -lactamase-stably-derepressed organisms were highly resistant (MIC <256 mg/L) to these antibiotics, whereas enzyme-basal strains and mutants were much more susceptible (MIC 1–16 mg/L). Imipenem also induced -lactamase production strongly at concentrations below its MIC, but was more stable than ampicillin and cefoxitin. It was active against enzyme-inducible and stably-derepressed organisms at 0·25–0·5 mg/L and against -lactamase-basal organisms at 0·06–0·25 mg/L. Thus the -lactamase afforded only very low-level protection against imipenem ; this appeared to be by a non-hydrolytic mechanism, with the enzyme binding to the antibiotic in a relatively stable complex. This complex, which probably was an intermediate in a hydrolytic pathway, was isolated by gelfiltration chromatography and shown to have a breakdown half-life of 47 ± 2 min. Cefotaxime, ceftriaxone and mezlocillin were labile to the I 8·4 -lactamase but induced -lactamase production weakly at concentrations below their MIC values. Consequently, -lactamase-inducible and -lactamase-basal organisms remained equally susceptible (MIC 0·06–4 mg/L), but stably-derepressed organisms were considerably more resistant (MIC>64 mg/L) to these antibiotics.

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1988-03-01
2022-01-20
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