Fosfomycin and tigecycline activity in extended-spectrum b-lactamase producing Enterobacteriaceae with reduced carbapenem susceptibility

Abstract number: P1170

Apfalter P., Zasmeta S., Graf A., Barousch W., Makristathis A., Hirschl A.

Objective: A recent Austrian susceptibility study on 401 ESBL-producing enterobacteriaceae revealed 16 (4%) and 43 (10.7%) strains (CLSI vs. EUCAST breakpoints, respectively) not fully susceptible to at least one carbapenem, the first choice agents in empiric ESBL therapy. The aim of this study was to test the in vitro activity of the new agent tigecycline and fosfomycin, which could provide therapeutic alternatives.

Methods: ESBL production was detected by CLSI methods and an expanded double disk diffusion synergy test in 401 non-duplicate enterobacteriaceae collected between June 04 and Dec 06. MICs were determined by means of Etest®. Strains not fully susceptible to one of the carbapenems were checked for the presence of metallo-b-lactamases and typed by means of random amplification of polymorphic DNA and enterobacterial repetitive intergenic consensus PCR.

Results: Meropenem was the only carbapenem not affected by reduced sensitivity. No metallo-b-lactamase production was detected in strains with reduced sensitivity to ertapenem or imipenem. According to CLSI (EUCAST) 62.5% (76.7%), 81.2% (74.4%), and 56.2% (46.5%) strains were susceptible to fosfomycin, tigecycline (FDA) and tigecycline (EUCAST), respectively. The figure displays the 16 CLSI criteria applied strains and their susceptibility to tigecycline and fosfomycin (height on y-axis stands for interpretative category: 1 space = susceptible; 2 spaces = intermediate susceptible; 3 spaces = resistant).

Strains with reduced crabpenem sensitivity according to CLSI

Conclusions: Fosfomycin and tigecycline can be therapeutic options in infections caused by ESBL-producing enterobacteriaceae with reduced sensitivity to carbapenems, but empiric use cannot be recommended and testing is mandatory. Applying EUCAST breakpoints affected significantly resistance data for tigecycline, for which every second strain out of this panel would have to be categorised as not fully susceptible. The clinical significance of this phenomenon caused by breakpoints defined by various committees remains to be clarified.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
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