883. Stool Toxin Concentrations Are Higher in Children with Baseline Severe Disease, Severe Outcomes, and Recurrence
Authors: Sandora Thomas J , Kociolek Larry K , Williams David N , Daugherty Kaitlyn , Geer Christine , Cuddemi Christine , Chen Xinhua , Xu Hua , Savage Timothy J , Banz Alice , Garey Kevin W , Gonzales-Luna Anne J , Kelly Ciaran P , Pollock Nira R 
Published: December 2022

Background

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

Methods

We performed a prospective cohort study from 2016-2019. Participants were inpatients ≤17 years old at two pediatric hospitals with diarrhea and positive C. difficile testing who received therapy. Patients were followed for 40 days after baseline stool sample for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence (resolution followed by new diarrhea and re-initiation of therapy). Baseline stool toxin A & B concentrations were measured using ultrasensitive single molecule array assay (cutoff for positive result = 20 pg/mL). Median baseline toxin concentrations were compared between groups using Wilcoxon tests.

Results

We enrolled 206 patients [median age 8.9 years (IQR, 4.7–13.2)]. Children with severe baseline disease by IDSA-SHEA criteria (n = 39) had higher median stool toxin A+B concentration than those without severe disease (n = 131) (2,912.6 vs. 500.5 pg/mL, P=0.05). Of the cohort, 40 (19%) had a severe outcome (4 primarily attributed to CDI, 19 with contribution from CDI, and 17 unrelated to CDI). Median toxin A+B concentration was non-significantly higher in children with a primarily-attributed severe outcome versus those without severe outcome (19,473 vs. 429.1 pg/mL, P=0.317) (Figure 1). Of 197 children with eligible data, recurrence occurred in 18 (9.1%); baseline toxin A+B concentration was significantly higher in patients with versus without recurrence (3,946.7 vs. 283.3 pg/mL, P=0.026) (Figure 2).

Conclusion

Higher stool toxin concentrations are present in children with baseline severe CDI, a CDI-attributable severe outcome, or recurrence compared with children without these presentations. Quantification of stool toxin concentration may be helpful in identifying severe CDI and predicting CDI outcomes, which could help guide decisions about clinical management.

Disclosures

Larry K. Kociolek, MD, MSCI, Merck: Grant/Research Support Timothy J. Savage, MD, MPH, MSc, UCB: Contract to Brigham and Women's Hospital Alice Banz, PhD, biomerieux: Simoa assays were performed by bioMerieux, and A.B. is an employee of bioMerieux Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|cidara: Advisor/Consultant|cidara: Grant/Research Support|Paratek: Grant/Research Support|Seres Health: Grant/Research Support|Summit: Grant/Research Support Ciaran P. Kelly, n/a, Artugen: Advisor/Consultant|Facile Therapeutics: Advisor/Consultant|Ferring Pharma: Advisor/Consultant|Finch: Advisor/Consultant|Finch: Advisor/Consultant|First Light Biosciences: Advisor/Consultant|First Light Biosciences: Ownership Interest|Milky Way Biosciences: Advisor/Consultant|Milky Way Biosciences: Grant/Research Support|Pfizer: Advisor/Consultant|Seres Therapeutics: Advisor/Consultant|Summit Therapeutics: Advisor/Consultant.