864. Increased C. difficile Cytotoxin activity in stool of immunocompromised patients is associated with increased antibiotic exposure
Session: Poster Abstract Session: Bacterial Infections: Pathogenesis and Immunity
Friday, October 9, 2015
Room: Poster Hall
  • FINALIDSA-CDI2015_NPs format.pdf (1.2 MB)
  • Background: Patients with C. difficile infection (CDI) present with a wide spectrum of illness, from mild diarrhea to life-threatening toxic megacolon, but current prediction models for poor outcomes are suboptimal. In particular, there is little data on prediction tools in immunocompromised patients or the effect of immune status on the course of disease. We hypothesize that cytotoxin activity in stool may correlate disease severity and outcome, and this could be influenced by immune status.

    Methods: We enrolled 50 subjects, 23 immunocompetent (NH) and 27 immunocompromised (IC) patients with acute symptoms of CDI and a positive stool C. diff PCR test (first episode or first recurrence). IC patients were neutropenic (11; 6 with hematologic or lymphoreticular CA), stem cell (5; 3 were also neutropenic) or solid organ transplant recipients (10), and patients on immunosuppressives (6; 2 were also neutropenic), including concomitant chemotherapy and high-dose corticosteroids. Aliquots of positive stool specimens are collected and filtrates prepared. Stool filtrates are serially diluted and the amount of cytotoxic activity determined using a tissue-culture cytotoxin assay. Age, WBC count, Cr, albumin, and number of bowel movements (BM) per day were also recorded.

    Results: A higher proportion of patients in the IC group had C. difficile toxin titers > 1:1,280 compared to NH patients (63 % vs 30 %, p = 0.02). We did post hoc analysis of the differences between groups by LSD showed that, the only IC group that contributed to the differences between groups were patients with neutropenia (mean titer 3,785 +/- 1,984 vs 1,598 +/- 2,371 for the NH group). Patients with neutropenia were more likely to be on concomitant antibiotics.

    Conclusion: The C. difficile cytotoxin titers in stool of IC patients were significantly higher compared to NH patients, but this was driven by higher titers in patients with neutropenia and not other immunocompromised groups. Patients with neutropenia were more likely to be receiving concomitant antibiotics than NH patients, solid organ transplant recipients, and other IC patients. This indicates the severity of disease in neutropenic patients is due to antibiotic pressure rather than a poor host response to C. difficile colitis.

    Jennifer Delacruz, MD, MS1, Fredy Chaparro-Rojas, MD2, Randee Estes, MT (A.S.C.P.)1, Natasha Pettit, PharmD3, Lindsay Petty, M.D.4, Kathleen Mullane, DO, FIDSA5 and David Pitrak, MD, FIDSA1, (1)Department of Medicine, Section of Infectious Diseases and Global Health, University of Chicago Hospitals, Chicago, IL, (2)Vidant Multispecialiaty Clinic, Tarboro, NC, (3)Pharmacy Services, The University of Chicago Medicine, Chicago, IL, (4)Infectious Diseases and Global Health, University of Chicago Medicine, Chicago, IL, (5)University of Chicago Medicine, Chicago, IL


    J. Delacruz, None

    F. Chaparro-Rojas, None

    R. Estes, None

    N. Pettit, None

    L. Petty, None

    K. Mullane, MERCK: Consultant and Investigator , Consulting fee and Research support
    Rebiotics: Investigator , Research support
    Summit: Investigator , Research support
    Seres: Investigator , Research support
    Viropharma -Shire: Investigator , Research support
    Novartis: Investigator , Research support
    Actelion: Investigator , Research support

    D. Pitrak, Gilead: Grant Investigator , Grant recipient
    ViroPharma: Grant Investigator , Grant recipient and Research grant
    Merck: Grant Investigator , Grant recipient and Research grant

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.