Quantity of Toxin in Stool Correlates with C. difficile Severity

Clostridioides difficile (syn. Clostridium difficile), also known as C. difficile, or C. diff are Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen.

Although C. difficile is commonly known as a hospital and antibiotic associated pathogen, at most one third of infections can be traced to transmission from an infected person in hospitals, and only a small number of antibiotics are directly associated with an elevated risk of developing a C. difficile infection (CDI). Pathogenic C. difficile strains produce multiple toxins.


Infectious Disease Specialists at the Beth Israel Deaconess Medical Center (Boston, MA, USA) and their colleagues enrolled 615 hospitalized adults (≥ 18 years) with CDI (acute diarrhea, positive stool Nucleic Acid Amplification Test (NAAT), and decision to treat). Baseline stool toxin A and B concentrations were measured by Simoa Single Molecule Array (Quanterix, Billerica, MA, USA). Subjects were classified by baseline CDI severity (four scoring methods) and outcomes within 40 days (death, ICU stay, colectomy, and recurrence).

The investigators reported that overall, the study showed that across all scoring systems, patients with severe baseline disease had higher stool toxin A and B concentrations than those without. 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) than subjects in whom CDI only contributed to the outcome (group 2, 163.2 pg/mL), subjects with severe outcome unrelated to CDI (group 3, 158.6 pg/mL), or no severe outcome (group 4, 209.5 pg/mL). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5%-66.1%). Individuals with recurrence had higher toxin A+B (2,266.8 pg/mL) than those without (154.0 pg/mL) and higher rates of detectable toxin (85.7% versus 64.0%).

Carolyn D. Alonso, MD, an Assistant Professor of Medicine and first author of the study, and her colleagues said, “This study lays the foundation for developing a highly accurate, single-step test to better diagnose C. difficile infection and predict clinical outcomes. Ultimately, we hope that our research will move the field toward development of a single-step test for C. difficile that can be easily deployed by clinicians without specific expertise in C. difficile diagnosis.”

The authors concluded that 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. The study was published on September 19, 2021 in the journal Clinical Infectious Diseases.

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Beth Israel Deaconess Medical Center
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