title: Chromosomal beta-lactamase expression and antibiotic resistance in Enterobacter cloacae.
abstract: The activities of beta-lactam antibiotics were compared against Enterobacter cloacae clinical isolates and mutants which had inducible, stably-derepressed, and basal expression of a pI 8.4 subtype of the Ia chromosomal beta-lactamase. These activities were correlated with the results of studies of the beta-lactamase-lability and beta-lactamase-inducer-power of the antibiotics. Cefoxitin and ampicillin were labile, and induced beta-lactamase production strongly at concentrations below their MIC values. Consequently, beta-lactamase-inducible and beta-lactamase-stably-derepressed organisms were highly resistant (MIC greater than 256 mg/L) to these antibiotics, whereas enzyme-basal strains and mutants were much more susceptible (MIC 1-16 mg/L). Imipenem also induced beta-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 beta-lactamase-basal organisms at 0.06-0.25 mg/L. Thus the beta-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 pI 8.4 beta-lactamase but induced beta-lactamase production weakly at concentrations below their MIC values. Consequently, beta-lactamase-inducible and beta-lactamase-basal organisms remained equally susceptible (MIC 0.06-4 mg/L), but stably-derepressed organisms were considerably more resistant (MIC greater than 64 mg/L) to these antibiotics.
authors.affiliation: Department of Medical Microbiology, London Hospital Medical College.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yang
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
authors.forename: R J
authors.initials: RJ
authors.lastname: Williams
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002876:Chromosomes, Bacterial / Q000502:physiology*; D004352:Drug Resistance, Microbial; D004754:Enterobacter / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D004755:Enterobacteriaceae / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D013045:Species Specificity; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases