title: Emergence of carbapenem-non-susceptible extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates at the university hospital of Tübingen, Germany.
abstract: The spread of Gram-negative bacteria with plasmid-borne extended-spectrum beta-lactamases (ESBLs) has become a worldwide problem. This study analysed a total of 366 ESBL-producing Enterobacteriaceae strains isolated from non-selected patient specimens at the university hospital of Tübingen in the period January 2003 to December 2007. Although the overall ESBL rate was comparatively low (1.6 %), the percentages of ESBL-producing Enterobacter spp. and Escherichia coli increased from 0.8 and 0.5 %, respectively, in 2003 to 4.6 and 3.8 % in 2007. In particular, the emergence was observed of one carbapenem-resistant ESBL-producing E. coli isolate and five carbapenem-non-susceptible ESBL-positive Klebsiella pneumoniae isolates, in two of which carbapenem resistance development was documented in vivo under a meropenem-containing antibiotic regime. The possible underlying mechanism for this carbapenem resistance in three of the K. pneumoniae isolates was loss of the Klebsiella porin channel protein OmpK36 as shown by PCR analysis. The remaining two K. pneumoniae isolates exhibited increased expression of a tripartite AcrAB-TolC efflux pump as demonstrated by SDS-PAGE and mass spectrometry analysis of bacterial outer-membrane extracts, which, in addition to other unknown mechanisms, may contribute towards increasing the carbapenem MIC values further. Carbapenem-non-susceptible ESBL isolates may pose a new problem in the future due to possible outbreak situations and limited antibiotic treatment options. Therefore, a systematic exploration of intestinal colonization with ESBL isolates should be reconsidered, at least for haemato-oncological departments from where four of the five carbapenem-non-susceptible ESBL isolates originated.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Eberhard Karls University of Tübingen, Elfriede-Aulhorn-Str. 6, D-72076 Tübingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gröbner
authors.affiliation: Max Planck Institute for Developmental Biology, Department I, Protein Evolution, Spemannstr. 35, D-72076 Tübingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Linke
authors.affiliation: Proteome Centre Tübingen, Interfaculty Institute of Cell Biology, University of Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schütz
authors.affiliation: Proteome Centre Tübingen, Interfaculty Institute of Cell Biology, University of Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fladerer
authors.affiliation: Proteome Centre Tübingen, Interfaculty Institute of Cell Biology, University of Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Madlung
authors.affiliation: Institute of Medical Microbiology and Hygiene, Eberhard Karls University of Tübingen, Elfriede-Aulhorn-Str. 6, D-72076 Tübingen, Germany.
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.affiliation: Robert Koch Institute, Burgstr. 37, D-38855 Wernigerode, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Witte
authors.affiliation: Robert Koch Institute, Burgstr. 37, D-38855 Wernigerode, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Pfeifer
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015780:Carbapenems / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D013058:Mass Spectrometry; D018272:Porins / Q000235:genetics / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D018272:Porins; D001618:beta-Lactamases