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Activities of tigecycline in combination with colistin or meropenem against KPC carbapenemase-producing Enterobacteriaceae by time-kill analysis

Abstract number: O361

Pournaras S., Neou E., Poulou A., Vrioni G., Tsakris A.

Objectives: Enterobacteriaceae producing KPC carbapenemases cause hospital infections often associated with therapeutic failures and increased mortality. The treatment of these infections usually requires the use of tigecycline or colistin as a last-resort drug. The objective of this study was to test the in vitro activity of tigecycline against KPC-producing Enterobacteriaceae.

Methods: The KPC-producing isolates comprised four Klebsiella pneumoniae, two Escherichia coli, one Enterobacter cloacae and one Serratia marcescens. The K. pneumoniae and E. coli isolates were randomly selected among those representing different clonal types. MICs were obtained using the macrodilution method in fresh Mueller–Hinton broth (MHB), before performing time-kill assays by inoculating 5x105 CFU/mL of the test organisms in 3 ml MHB. E. coli ATCC 25922 was used as control. Antibiotics (tigecycline, colistin and meropenem as single agents and in combinations) were added at concentrations 1x and 2x the MIC for each isolate. Aliquots were removed at times 0, 2 h, 4 h, 6 h, 8 h, 16 h and 24 h post-inoculation, serially diluted and plated on MH agar plates for enumeration of viable colonies. Each time-kill experiment was performed twice. As bactericidal activity was defined a geqslant R: gt-or-equal, slanted3 log10 CFU/mL reduction in viable cells with respect to the original inoculum.

Results: Macrodilution MIC values were 0.25 to 2 mg/L for tigecycline, 0.5 to 1 mg/L for colistin and 2 to 16 mg/L for meropenem. In time-kill assays, tigecycline and meropenem as single agents were mostly bacteriostatic for the first 6–8 hours of incubation with bacterial regrowth to follow, while colistin alone was ineffective. The tigecycline plus colistin combination was in most cases bactericidal after 4 to 8 h of incubation and in some cases also synergistic compared with tigecycline alone, although bacterial regrowth was observed after 8 to 16 h. The tigecycline plus meropenem combination was in most cases also bactericidal after 4 to 6 h of incubation and thereafter regrowth was observed.

Conclusion: The results of the present study indicate that tigecycline alone could be a therapeutic option for infections due to multidrug resistant KPC producers when bacteriostatic activity is adequate or in combination with colistin or meropenem when bactericidal activity is necessary. Additional in vivo tests may be warranted to fully assess the killing kinetics of tigecycline against KPC producers when the immune system is competent.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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