Emergence of carbapenem-non-susceptible extended-spectrum b-lactamase-producing Klebsiella pneumoniae isolates at the university hospital of Tü bingen, Germany The spread of Gram-negative bacteria with plasmid-borne extended-spectrum b-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 Tü bingen 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 meropenemcontaining 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.
INTRODUCTIONIn contrast to the USA and the Western Pacific area, the prevalence of extended-spectrum b-lactamases (ESBLs) in Germany was comparably low in 2001 (8.2 % of Klebsiella pneumoniae and 0.8 % of Escherichia coli isolates; Sturenburg & Mack, 2003). However, the prevalence of ESBL-producing Gram-negative bacteria is increasing, both in hospitals and in the community (Sturenburg & Mack, 2003;Pitout et al., 2005).ESBLs confer resistance to amino-and ureidopenicillins, oximino-cephalosporins and monobactams. As co-resistance to non-b-lactam antimicrobials is common among ESBL isolates, the treatment options are limited. Among the E. coli and K. pneumoniae isolates predominantly found to produce ESBLs in Europe, carbapenem-non-susceptible isolates are becoming more widespread (
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