Ultrasensitive and Quantitative Toxin Measurement Correlates With Baseline Severity, Severe Outcomes, and Recurrence Among Hospitalized Patients With Clostridioides difficile Infection

• Published in: Clinical infectious diseases Vol. 74; no. 12; pp. 2142 - 2149
• Main Authors: Alonso, Carolyn D, Kelly, Ciarán P, Garey, Kevin W, Gonzales-Luna, Anne J, Williams, David, Daugherty, Kaitlyn, Cuddemi, Christine, Villafuerte-Gálvez, Javier, White, Nicole C, Chen, Xinhua, Xu, Hua, Sprague, Rebecca, Barrett, Caitlin, Miller, Mark, Foussadier, Agnès, Lantz, Aude, Banz, Alice, Pollock, Nira R
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 06.07.2022
• Subjects: Major and Commentaries; recurrence; clinical outcomes; toxin concentration; Clostridioides difficile
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciab826

Abstract Background Stool toxin concentrations may impact Clostridioides difficile infection (CDI) severity and outcomes. We correlated fecal C difficile toxin concentrations, measured by an ultrasensitive and quantitative assay, with CDI baseline severity, attributable outcomes, and recurrence. Methods We enrolled 615 hospitalized adults (≥18 years) with CDI (acute diarrhea, positive stool nucleic acid amplification testing, and decision to treat). Baseline stool toxin A and B concentrations were measured by single molecule array. Subjects were classified by baseline CDI severity (4 scoring methods) and outcomes within 40 days (death, intensive care unit stay, colectomy, and recurrence). Results Among 615 patients (median, 68.0 years), in all scoring systems, subjects with severe baseline disease had higher stool toxin A+B concentrations than those without (P < .01). Nineteen subjects (3.1%) had a severe outcome primarily attributed to CDI (group 1). This group had higher median toxin A+B (14 303 pg/mL [interquartile range, 416.0, 141 967]) than subjects in whom CDI only contributed to the outcome (group 2, 163.2 pg/mL [0.0, 8423.3]), subjects with severe outcome unrelated to CDI (group 3, 158.6 pg/mL [0.0, 1795.2]), or no severe outcome (group 4, 209.5 pg/mL [0.0, 8566.3]) (P = .003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2–4 (60.5%–66.1%) (P = .02). Individuals with recurrence had higher toxin A+B (2266.8 pg/mL [188.8, 29411]) than those without (154.0 pg/mL [0.0, 5864.3]) (P < .001) and higher rates of detectable toxin (85.7% versus 64.0%, P = .004). Conclusions In CDI patients, ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course. In this prospective cohort study of adults with C difficile infection (CDI), ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course.