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Genotyping of Gram-negative uropathogens isolated pre and post-treatment from subjects in a doripenem clinical trial for complicated urinary tract infections

Abstract number: O76

Davies T., Shang W., Redman R., Bush K., Flamm R.

Objectives: Doripenem (DOR) a parenteral carbapenem was approved in the US for treatment of complicated intraabdominal and complicated urinary tract infections including pyelonephritis (cUTI). In a cUTI trial comparing DOR and IV levofloxacin (LVX), the microbiologic cure rate at test of cure (TOC, day 6–11 post therapy) for the microbiologically evaluable population was 82.1% (230 / 280) in the DOR group and 83.4% (221 / 265) in the LVX group. Gram-negative pathogens isolated from the same subject pre- and post-treatment (microbiological failures) were genotyped to determine if the pre-treatment isolate persisted or if a new infection occurred.

Methods: Baseline Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa isolates were compared to TOC or late follow-up (LFU, day 28–35 post therapy) isolates by pulsed-field gel electrophoresis (PFGE). TOC and LFU isolates with leqslant R: less-than-or-eq, slant6 DNA band differences to the matched baseline isolate were classified as persistent infections; isolates with >6 differences were considered to be a different strain (new infection). Isolates producing smears by PFGE were non-typeable (NT).

Results: For P. mirabilis, P. aeruginosa, and K. pneumoniae microbiologic failures in the DOR and LVX treatment groups were usually due to persistence of the baseline pathogen. For E. coli, microbiologic failures due to a new infection were higher in the DOR treatment group (44%) then the LVX group (29%) for TOC isolates. Prevalence of new E. coli infections increased at LFU to about two-thirds for both treatment groups. When a LVX-resistant E. coli was present at baseline, microbiologic failures due to persistence was 78% and 57% in the LVX and DOR treatment groups, respectively.

Conclusion: In a cUTI trial, microbiologic failures in the DOR and LVX treatment groups for P. mirabilis, P. aeruginosa, and K. pneumoniae were usually (>80%) due to persistence of the baseline isolate. E. coli failures were due to replacement of the baseline isolate (new infection) in >50% of the cases.

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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