1. In-vitro selection of porin-deficient mutants of two strains of Klebsiella pneumoniae with reduced susceptibilities to meropenem, but not to imipenem.
- Author
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Pragai Z and Nagy E
- Subjects
- Drug Resistance, Microbial genetics, Electrophoresis, Polyacrylamide Gel, Humans, Klebsiella Infections microbiology, Klebsiella pneumoniae metabolism, Meropenem, Microbial Sensitivity Tests, Mutation, Polymerase Chain Reaction methods, Porins genetics, beta-Lactamases metabolism, Imipenem pharmacology, Klebsiella pneumoniae drug effects, Klebsiella pneumoniae genetics, Porins metabolism, Thienamycins pharmacology
- Abstract
We have evaluated the ability of imipenem and meropenem to select, in vitro, resistant mutants of two clinical isolates of Klebsiella pneumoniae producing both SHV and TEM beta-lactamases. Only meropenem selected mutants of both isolates for which the MICs of meropenem, but not imipenem, were markedly higher than those for the parent strains; the MICs of several other beta-lactam antibiotics, including beta-lactam/beta-lactamase inhibitor combinations, for these mutants were also higher than those for the parent strains. In contrast, the MICs for the imipenem-selected mutants were the same as, or similar to, those for the parent strains. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis revealed that an outer membrane protein in both parent strains was absent in the meropenem-selected mutants, but not in the imipenem-selected mutants. This protein is likely to be a porin, the absence of which is presumably associated with impaired beta-lactam permeability and, therefore, the reduced susceptibilities to these antibiotics exhibited by the mutant strains. We believe that this is the first report of the in-vitro selection of porin-deficient mutants of K. pneumoniae following exposure to meropenem.
- Published
- 1998
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