Emergence of carbapenem-non-susceptible extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates at the university hospital of Tubingen, Germany

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 Tubingen 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-ToIC 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.