title: Combined porin loss and extended spectrum beta-lactamase production is associated with an increasing imipenem minimal inhibitory concentration in clinical Klebsiella pneumoniae strains.
abstract: For this study, 150 clinical isolates of Klebsiella pneumoniae were collected from one hospital in Beijing, China, and assayed for minimal inhibitory concentration (MIC) of imipenem. To elucidate the mechanisms responsible for imipenem MIC variation among extended-spectrum beta-lactamase (ESBL)-positive and -negative K. pneumoniae strains, a variety of beta-lactamase genes (bla(TEM), bla(CTX-M), bla(SHV), and bla(OXA)) were screened by polymerase chain reaction (PCR). The outer membrane profile and expression of related genes (ompK35 and ompK36) then were analyzed and evaluated, respectively. None of the tested isolates were clinically resistant to imipenem, but the range of MICs among ESBL-positive and -negative strains was significantly different. Deficiency in the expression of outer membrane proteins (OmpK35,36) was observed in some of both ESBL-positive(17.6%) and -negative strains (10.9%), but only the ESBL-positive strains depressed by the expression of ompK35/36 had an increased MIC of imipenem (>or=0.5 mg/l). These results confirmed that the combination of SHV-1, CTX-M-3, CTX-M-14, TEM-1, or OXA-11 production and reduced expression of ompK35/36 may not result in clinical resistance to imipenem but does correlate with increasing imipenem MIC.
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Xicheng District, Beijing 100044, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002681:China / Q000453:epidemiology; D024881:Drug Resistance, Bacterial; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D007710:Klebsiella Infections / Q000453:epidemiology / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000096:biosynthesis*; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C119261:OmpK35 porin, Klebsiella pneumoniae; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins; D015378:Imipenem; D001618:beta-Lactamases