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2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes

BACKGROUND: The 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 eo...

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Autores principales: Carlson, Travis J, Endres, Bradley T, Le Pham, Julie, Gonzales-Luna, Anne J, Alnezary, Faris S, Nebo, Kimberly, Miranda, Julie, Begum, Khurshida, Alam, M Jahangir, Garey, Kevin W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810537/
http://dx.doi.org/10.1093/ofid/ofz360.2076
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author Carlson, Travis J
Endres, Bradley T
Le Pham, Julie
Gonzales-Luna, Anne J
Alnezary, Faris S
Nebo, Kimberly
Miranda, Julie
Begum, Khurshida
Alam, M Jahangir
Garey, Kevin W
author_facet Carlson, Travis J
Endres, Bradley T
Le Pham, Julie
Gonzales-Luna, Anne J
Alnezary, Faris S
Nebo, Kimberly
Miranda, Julie
Begum, Khurshida
Alam, M Jahangir
Garey, Kevin W
author_sort Carlson, Travis J
collection PubMed
description BACKGROUND: The 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. METHODS: This 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. RESULTS: A 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). CONCLUSION: This 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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spelling pubmed-68105372019-10-28 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes Carlson, Travis J Endres, Bradley T Le Pham, Julie Gonzales-Luna, Anne J Alnezary, Faris S Nebo, Kimberly Miranda, Julie Begum, Khurshida Alam, M Jahangir Garey, Kevin W Open Forum Infect Dis Abstracts BACKGROUND: The 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. METHODS: This 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. RESULTS: A 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). CONCLUSION: This 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. Oxford University Press 2019-10-23 /pmc/articles/PMC6810537/ http://dx.doi.org/10.1093/ofid/ofz360.2076 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Carlson, Travis J
Endres, Bradley T
Le Pham, Julie
Gonzales-Luna, Anne J
Alnezary, Faris S
Nebo, Kimberly
Miranda, Julie
Begum, Khurshida
Alam, M Jahangir
Garey, Kevin W
2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes
title 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes
title_full 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes
title_fullStr 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes
title_full_unstemmed 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes
title_short 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes
title_sort 2398. effect of eosinopenia and binary toxin on clostridioides difficile infection clinical outcomes
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810537/
http://dx.doi.org/10.1093/ofid/ofz360.2076
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