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In vitro bactericidal effect of imipenem, meropenem and piperacillin/tazobactam against b-lactam-resistant Pseudomonas aeruginosa strains and ESBL-producing Enterobacteriaceae

Abstract number: P1167

Muller-Serieys C., Merens A., Cavallo J.D., Laussucq C., Joly-Guillou M.L., Roussel-Delvallez M.

Objectives: In France, the spread of acquired multiresistance in P. aeruginosa (Pa) and Enterobacteriaceae (Eb) has become a great concern. Infections caused by these bacteria require early treatment with bactericidal antibiotics. Carbapenems are often the last resort alternative. The goal of this study was to compare the in vitro kill-rates of imipenem (IPM), meropenem (MPM) and piperacillin/tazobactam (PTZ) against 7 Pa strains with different b-lactam resistance mechanisms and 4 ESBL-producing Eb.

Material and Methods: The standard time-kill method was used to investigate the bactericidal activity of IPM, MPM and PTZ. The concentrations tested were the breakpoints defined by EUCAST for Eb (2 and 8 mg/L for IPM and MPM) and for Pa (4 and 8 mg/L for IPM, 2 and 8 mg/L for MPM). For PTZ: 16/4 mg/L was used for Pa and 8/4 mg/L for Eb. The following strains were studied: (i) P. aeruginosa ATCC 27853, E. coli ATCC 25922 as reference strains, (ii) seven Pa: efflux (overexpression of MexAB/OprM pump), mutation of OprD2, carbenicillinase PSE-1, extended-spectrum b-lactamase PER-1, carbapenemases IMP-1 and VIM-2 and overexpressed constitutive cephalosporinase, (iii) four ESBL Eb: K. pneumoniae CTX-1 and SHV-2, E. aerogenes TEM-24, E. coli CTX-M15. Bactericidal effect was defined by a 3 Log10 CFU/mL decrease in viable counts.

Results: A bactericidal effect was obtained at 6–8 hours for IPM and MPM at 8 mg/L for all Pa strains except for those with acquired resistance mechanisms to carbapenems (mutation of OprD2 and carbapenemases). The use of lower concentrations of IPM (4 mg/L) or MPM (2 mg/L) resulted in a decrease or abolition of bactericidal effect and a frequent regrowth after 8 h. PTZ was bactericidal only for the strain displaying efflux resistance mechanism. For ESBL-producing Eb, both carbapenems were bactericidal against all strains in 4–8 hours at 2 mg/L and 8 mg/L. MEM was more rapidly bactericidal than IPM (killing activity at 2 hours for 3 strains/4 at 8 mg/L). No regrowth was observed. PTZ was not bactericidal and only a 2 Log10 decrease of inoculum was obtained.

Conclusion: IPM and MPM achieved a rapid killing activity against the most prevalent ESBL Enterobacteriaceae in France and provided a bactericidal activity at 8 mg/L against all P. aeruginosa strains without OprD2 mutation or carbapenemase.

Session Details

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