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

Abstract

The spread of Gram-negative bacteria with plasmid-borne extended-spectrumβ-lactamases (ESBLs) has become a worldwide problem. This study analysed a total of 366 ESBL-producingEnterobacteriaceaestrains 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-producingEnterobacterspp. andEscherichia coliincreased 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-producingE. coliisolate and five carbapenem-non-susceptible ESBL-positiveKlebsiella pneumoniaeisolates, in two of which carbapenem resistance development was documentedin vivounder a meropenem-containing antibiotic regime. The possible underlying mechanism for this carbapenem resistance in three of theK. pneumoniaeisolates was loss of theKlebsiellaporin channel protein OmpK36 as shown by PCR analysis. The remaining twoK. pneumoniaeisolates 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.