1251. Change in bacterial diversity of fecal microbiota drives mortality in a hamster model of antibiotic-induced Clostridium difficile colitis
Session: Poster Abstract Session: C. difficile: From the Bench to Bedside
Friday, October 6, 2017
Room: Poster Hall CD
Posters
  • 2017.09.12_posterIDWeek.pdf (1.1 MB)
  • Background: C. difficile (C diff) infection results from antibiotic-induced changes in colonic microbiota. DAV131A, an oral adsorbent-based product, can sequester antibiotic (AB) residues in the gut and reduce mortality in a hamster model of moxifloxacin (MXF) or clindamycin (CM) induced C diffcolitis. We studied the link between changes of the bacterial diversity within the fecal microbiota and mortality in this model.

    Methods: Male Syrian hamsters were administered 30 mg/kg MXF or 5 mg/kg CM subcutaneously once a day for 5 days (D1 to D5) and orally infected at D3 with 104 C diffspores. They were orally administered various doses of DAV131A (0, and 200 to 900 mg/kg twice a day), from D1 to D8. Survival was monitored up to D16 and feces were collected (D1 & D3) to characterize the microbiota by 16S rRNA gene profiling. Changes of various α- (Shannon, Observed OTUs and Chao1) and β- (Bray-Curtis dissimilarity and [un]weighted UniFrac) diversity indices between D1 & D3 were obtained for each animal. We analyzed links between (i) DAV131A dose and changes of bacterial diversity and (ii) changes of bacterial diversity and mortality using non parametric tests and logistic regression.

    Results: Data from 70 and 60 animals were available in the MXF and CM studies, among which 10 and 28 died, respectively. Increasing doses of DAV131A reduced mortality from 100% to 0% and reduced changes in bacterial diversity of the fecal microbiota. Very strong predictors of mortality were changes in Shannon and unweighted UniFrac indices, which were markedly less affected in hamsters who survived (see table below median (min; max) according to vital status & area under the ROC curve, AUROC).

     

    Died

    Survived

    p

    AUROC [95%CI]

    MXF

    n

    10

    60

    Shannon

    -1.7 (-3.0; -1.0)

    -1.0 (-1.9; 0.1)

    <10-4

    0.91 [0.80; 0.99]

    Unweighted UniFrac

    0.61 (0.56; 0.76)

    0.51 (0.37; 0.65)

    <10-6

    0.95 [0.89; 0.99]

    CM

    n

    28

    32

    Shannon

    -2.2 (-4.3; -0.4)

    -1.1 (-2.6; 0.0)

    <10-7

    0.88 [0.78; 0.96]

    Unweighted UniFrac

    0.71 (0.59; 0.84)

    0.60 (0.49; 0.68)

    <10-10

    0.94 [0.87; 0.98]

    Conclusion: The extent of AB-induced changes in gut bacterial diversity correlated with increased mortality in a hamster model of C diff colitis. Higher doses of DAV131A protected fecal microbiota disruption and hence mortality.

    Charles Burdet, M.D., MPH1, Thu Thuy Nguyen, PhD2, Nathalie Saint-Lu, PhD3, Sakina Sayah-Jeanne, PhD3, Perrine Hugon, PharmD, PhD3, Frédérique Sablier-Gallis, PharmD, PhD3, Stéphanie Ferreira, PhD4, Antoine Andremont, MD, PhD1, France Mentré, MD, PhD1 and Jean De Gunzburg, PhD3, (1)INSERM & Paris Diderot University, IAME, UMR 1137; AP-HP, Bichat Hospital, Paris, France, (2)INSERM & Paris Diderot University, IAME, UMR 1137, Paris, France, (3)Da Volterra, Paris, France, (4)Genoscreen, Lille, France

    Disclosures:

    C. Burdet, Da Volterra: Consultant and Research Contractor , Consulting fee

    T. T. Nguyen, None

    N. Saint-Lu, Da Volterra: Employee , Salary

    S. Sayah-Jeanne, Da Volterra: Employee , Salary

    P. Hugon, Da Volterra: Employee , Salary

    F. Sablier-Gallis, Da Volterra: Employee , Salary

    S. Ferreira, Genoscreen: Employee , Salary

    A. Andremont, Da Volterra: Consultant , Consulting fee

    F. Mentré, Da Volterra: Consultant and Research Contractor , Consulting fee

    J. De Gunzburg, Da Volterra: Consultant and Shareholder , Consulting fee

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