Researchers Find Ultrasensitive Stool Toxin Detection and Concentration Correlated with Severe Baseline In Hospitalized Patients With C. difficile Infection

Ultrasensitive and quantitative toxin measurement correlates with baseline severity, severe outcomes, and recurrence among hospitalized patients with Clostridioides difficile infection




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.


We enrolled 615 hospitalized adults (≥ 18y) with CDI (acute diarrhea, positive stool NAAT, and decision to treat). Baseline stool toxin A and B concentrations were measured by Single Molecule Array. Subjects were classified by baseline CDI severity (four scoring methods) and outcomes within 40 days (death, ICU stay, colectomy, and recurrence).


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<0.01). 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 (IQR 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=0.003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5-66.1%)(P=0.02). 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<0.001) and higher rates of detectable toxin (85.7% versus 64.0%, P=0.004).


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.