1409. Whole Genome Sequencing Demonstrates Fidaxomicin Prevents C. difficile Relapse and Reinfection
Session: Poster Abstract Session: Clostridium difficile
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • Fdx_Recurrence_Final.pdf (2.9 MB)
  • Background: Clostridium difficile infection (CDI) recurrence is reduced following initial treatment with fidaxomicin (FDX) compared to vancomycin (VAN), possibly due to less disruption of the intestinal microbiome. Using whole genome sequencing (WGS) we investigated whether FDX reduced recurrence in pivotal Phase III trials by preventing relapse of the same infection, reinfection or both.

    Methods: Paired isolates were available from 90/199 trial patients with recurrent CDI (27FDX, 63VAN) and underwent WGS using the Illumina HiSeq. Single nucleotide variants (SNVs) were determined between each isolate pair. Given rates of C. difficile within-host diversity and evolution, samples 2 SNVs apart were considered relapses, samples >10 SNVs apart re-infection, and those with 3-10 SNVs (or without WGS) indeterminate. The impact of FDX vs VAN on the cumulative incidence of relapse, re-infection, and indeterminate recurrence was compared using competing risks survival analysis.

    Results: Overall, 73/90 (81%) sequenced recurrences were within 2 SNVs consistent with relapse, 3 had 3-10 SNVs between isolates, and 14 (16%) had >10 SNVs suggesting re-infection. Relapse 2 SNVs occurred in 22/494 (4%) FDX vs 51/496 (10%) VAN patients (competing risks hazard ratio (crHR)=0.41 [95%CI 0.25-0.68] p=0.0005). Most relapses occurred within 2 weeks post treatment. 3 (0.6%) FDX vs 11 (2%) VAN patients had a re-infection (>10 SNVs) (crHR=0.27 [0.08-0.96] p=0.04) (Figure). 43 (9%) FDX vs 69 (14%) VAN patients had indeterminate recurrence (crHR=0.59 [0.40-0.96] p=0.007).

    Conclusion: Fidaxomicin reduces CDI recurrence by preventing both relapse of the original infection and re-infection.

    Description: Macintosh HD:Users:davideyre:Dropbox:C_Diff:Optimer:icaac2013_fdx_prevents_relapse_reinfection.ppt.pdf

    David Eyre, BM BCh1, Farah Babakhani, PhD2, David Griffiths, BSc1, Jaime Seddon, BS2, Tim Peto, DPhil1, A. Sarah Walker, PhD1 and Derrick Crook, MB BCh1, (1)National Institute for Health Research Oxford Biomedical Research Centre, Oxford, United Kingdom, (2)Optimer Pharmaceuticals, San Diego, CA

    Disclosures:

    D. Eyre, None

    F. Babakhani, Optimer Pharmaceuticals: Employee, Salary

    D. Griffiths, None

    J. Seddon, Optimer Pharmaceuticals: Employee, Salary

    T. Peto, Optimer Pharmaceuticals: Investigator and Scientific Advisor, Consulting fee and Research support

    A. S. Walker, None

    D. Crook, Optimer Pharmaceuticals: Investigator and Scientific Advisor, Consulting fee and Research support

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