Abstract

BackgroundThe ability of Clostridioides difficile to cause clinical disease in humans is dependent on toxin production. Significantly fewer eosinophils are seen in the peripheral blood of mice infected with a binary toxin positive (CDT+) C. difficile strain. Furthermore, the presence of CDT and eosinopenia have separately been associated with increased mortality in humans with C. difficile infection (CDI). We hypothesized that CDI due to a CDT+ C. difficile strain accompanied by peripheral eosinopenia would be associated with higher odds of inpatient mortality.MethodsThis multicenter, retrospective cohort study included all patients ≥ 18 years of age with toxigenic CDI in which specimen ribotype data were available as part of our ongoing surveillance study. The cohort was stratified by eosinophil count (0.0 cells/μL vs. > 0.0 cells/μL). The primary outcome was inpatient mortality. A logistic regression model was developed modeling inpatient mortality as a function of the available patient covariates. All P-values were from 2-sided tests, and results were deemed statistically significant at P < 0.05.ResultsA total of 688 patients from 13 institutions in six cities were included. Of those, 132 had a baseline eosinophil count of 0.0 cells/µL and 556 had a baseline eosinophil count > 0.0 cells/µL. While the odds of inpatient mortality were higher among patients with eosinopenia and those infected with a CDT+ ribotype, the combination of these variables remained an independent predictor of inpatient mortality after adjusting for CCI score, WBC count, and serum albumin level (OR, 7.84; 95% CI, 1.85–33.20; P = 0.005).ConclusionThis is the first attempt to study the in vivo relationship between CDT presence, human immune response, and CDI clinical outcome. We identified an association between CDT presence with concomitant eosinopenia and worsened CDI outcomes. Healthcare facilities should consider identifying this important subset of patients at the time of CDI diagnosis. Future CDI drug development might benefit from targeting C. difficile properties that impair host immune response, which may in turn decrease adverse clinical outcomes associated with this disease.Disclosures All authors: No reported disclosures.

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