In-vitro selection of porin-deficient mutants of two strains of Klebsiellapneumoniae with reduced susceptibilities to meropenem, but not to imipenem

We have evaluated the ability of imipenem and meropenem to select, in vitro , resistant mutants of two clinical isolates of Klebsiella pneumoniae produ cing both SHV and TEM beta-lactamases. Only meropenem selected mutants of b oth isolates for which the MICs of meropenem, but not imipenem, were marked ly higher than those for the parent strains; the MICs of several other beta -lactam antibiotics, including beta-lactam/beta-lactamase inhibitor combina tions, 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-polya crylamide gel electrophoresis analysis revealed that an outer membrane prot ein in both parent strains was absent in the meropenem-selected mutants, bu t not in the imipenem-selected mutants. This protein is likely to be a pori n, the absence of which is presumably associated with impaired beta-lactam permeability and, therefore, the reduced susceptibilities to these antibiot ics exhibited by the mutant strains. We believe that this is the first repo rt of the in-vitro selection of porin-deficient mutants of K. pneumoniae fo llowing exposure to meropenem.