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Baseline stool toxin concentration is associated with risk of recurrence in children with Clostridioides difficile infection

Published online by Cambridge University Press:  10 January 2023

Thomas J. Sandora Open the ORCID record for Thomas J. Sandora [Opens in a new window] ,
Larry K. Kociolek ,
David N. Williams Open the ORCID record for David N. Williams [Opens in a new window] ,
Kaitlyn Daugherty ,
Christine Geer ,
Christine Cuddemi ,
Xinhua Chen ,
Hua Xu ,
Timothy J. Savage Open the ORCID record for Timothy J. Savage [Opens in a new window]  and
Alice Banz
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Thomas J. Sandora*
Affiliation:
Division of Infectious Diseases, Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts, United States Harvard Medical School, Boston, Massachusetts, United States
Larry K. Kociolek
Affiliation:
Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, United States Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
David N. Williams
Affiliation:
Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, Massachusetts, United States
Kaitlyn Daugherty
Affiliation:
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center Boston, Massachusetts, United States
Christine Geer
Affiliation:
Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, Massachusetts, United States Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center Boston, Massachusetts, United States
Christine Cuddemi
Affiliation:
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center Boston, Massachusetts, United States
Xinhua Chen
Affiliation:
Harvard Medical School, Boston, Massachusetts, United States Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center Boston, Massachusetts, United States
Hua Xu
Affiliation:
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center Boston, Massachusetts, United States
Timothy J. Savage
Affiliation:
Division of Infectious Diseases, Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts, United States Harvard Medical School, Boston, Massachusetts, United States Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States
Alice Banz
Affiliation:
bioMerieux, Marcy L’Etoile, France
Kevin W. Garey
Affiliation:
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, United States
Anne J. Gonzales-Luna
Affiliation:
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, United States
Ciarán P. Kelly
Affiliation:
Harvard Medical School, Boston, Massachusetts, United States Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center Boston, Massachusetts, United States
Nira R. Pollock
Affiliation:
Harvard Medical School, Boston, Massachusetts, United States Department of Laboratory Medicine, Boston Children’s Hospital, Boston, Massachusetts, United States Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
*
Author for correspondence: Thomas J. Sandora, E-mail: thomas.sandora@childrens.harvard.edu
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Abstract

Background:

In adults with Clostridioides difficile infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI.

Methods:

We conducted a prospective cohort study of inpatients aged 2–17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available.

Results:

We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; P = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; P = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL (P = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL (P < .001).

Conclusions:

Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 44 , Issue 9 , September 2023 , pp. 1403 - 1409
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Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

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Footnotes

PREVIOUS PRESENTATION. These data were presented in part as an oral abstract at IDWeek 2022, on October 21, 2022, in Washington, DC.

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