1359. Stool Cytotoxicity Activity Correlates with Immune Competency in Patients with C. difficile Infection
Session: Poster Abstract Session: Clostridium difficile
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
  • Abstract#40610.pdf (913.4 kB)
  • Background: Patients with C. difficileinfection (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. 

    Highly virulent strains of C. difficile characterized by increased cytotoxin production have been associated with an increased risk of complications and mortality, indicating the amount of toxin is an important disease determinant. The cytotoxicity activity in stool is the sum of organism load, toxin production, and host response.  We hypothesize that cytotoxin activity in stool may correlate disease severity and outcome.

    Methods: Our goal is to enroll 100 subjects, 50 immunocompetent (NL)and 50 immunocompromised (IC), with acute symptoms of CDI and a positive stool C. diff PCR test consistent with CDI (first episode or first recurrence). IC patients are defined as neutropenics, stem cell or solid organ transplant recipients, patients with advanced HIV infection, and patients on immunosuppressives, including 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:   To date, 22 patients have been enrolled, 9 NL (40.9%) and 13 IC (59.0%). A higher proportion of patients in the IC group had C. difficile toxin titers >/= 1:5,120 compared to NL patients (76.9% vs 11.1%, p = 0.014). High titers did not correlate with number of BMs or other clinical parameters or scores that have been associated disease severity or poor outcomes.    

    Conclusion: The C. difficile cytotoxin titers in stool of IC patients are significantly higher compared to NL patients. The host response to C. difficile and cytotoxin may be important in the course of CDI and responses to therapy.  Further study is needed to see if high cytotoxin titers correlate with disease severity or clinical outcomes.  Stool cytotoxicity could help guide clinical management and/or clinical trial design. 

    Fredy Chaparro-Rojas, MD1, Jennifer Delacruz, MD1, Randee Estes, BS1, Kathleen Mullane, DO, FIDSA1, David Pitrak, MD1 and University of Chicago Hospitals, Chicago, IL, (1)Department of Medicine, Section of Infectious Diseases and Global Health, University of Chicago Hospitals, Chicago, IL


    F. Chaparro-Rojas, None

    J. Delacruz, None

    R. Estes, None

    K. Mullane, ViroPharma: Grant Investigator, Grant recipient

    D. Pitrak, ViroPharma: Investigator, Grant recipient

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