Higher Stool Toxin Concentrations Increase Severity of Clostridioides Difficile Infection


For the first time, investigators proved that a higher presence of Clostridioides difficile bacteria and toxins cause a more severe infection.

Stool Toxin Concentrations Directly Correlate to Severity of Clostridioides Difficile Infection   For the first time, investigators proved that a higher presence of Clostridioides difficile (C. diff) bacteria and toxins cause a more severe infection.

Clostridioides difficile is a bacterium that causes nearly half a million infections and $1 billion in healthcare costs each year. Clostridioides difficile infection (CDI) most commonly affects individuals who are older and/or have weakened immune systems, causing diarrhea and inflammation of the large intestine. Hospital patients who recently completed an antibiotics prescription are also high-risk for CDI.

C diff is highly prevalent in and outside of healthcare settings, but healthy people can carry the bacterium with no illness or symptoms. There are several tests that can detect the presence of C diff, such as the nucleic acid amplification test (NAAT), but these do not distinguish between infection and colonization.

Investigators for the Beth Israel Deaconess Medical Center (BIDMC) sought to develop an ultrasensitive and quantitative immunotoxin assay. The assay was based on single molecule array technology and qualified stool concentrations ≥20 pg/mL for toxin A or B as positive.

Until this study, published in Clinical Infectious Diseases, no research had established a quantitative relationship between bacterium concentration and disease severity.

In the study, investigators enrolled 615 adults hospitalized with CDI at either BIDMC or the Texas Medical Center in Houston. The average age of the participants was 68 years. All patients had acute diarrhea, a positive (NAAT), and had initiated CDI therapy. Investigators tracked the patients for 40 days after the onset of CDI, collecting stool samples and monitoring symptoms and recovery.

The results showed what has been suspected but never confirmed: individuals with severe baseline disease had higher relative stool A+B toxin concentrations. 19 subjects (3.1%) had a severe CDI outcome, and they 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 [163.2 pg/mL (0.0, 8423.3)], subjects with severe outcome unrelated to CDI [158.6 pg/mL (0.0, 1795.2)], and subjects with no severe outcome [209.5 pg/mL (0.0, 8566.3)](P=0.003). Additionally, investigators found that the 19 subjects with severe CDI outcome had significantly more detectable toxin (94.7%) than the other patients (60.5-66.1%)(P=0.02).

Stool toxin detection and concentration consistently indicated severe CDI-attributable outcomes and recurrence. Patients with CDI recurrence had higher toxin A+B [2266.8 pg/mL(188.8, 29411)] than those with no recurrence [154.0 pg/mL(0.0, 5864.3)](P<0.001). Subjects with recurrence also had higher rates of detectable toxin (85.7% versus 64.0%, P=0.004).

Senior/corresponding author Nira R. Pollock, MD, PhD, of the Division of Infectious Diseases at BIDMC, the associate medical director of the Infectious Diseases Diagnostic Laboratory at Boston Children’s Hospital, and associate professor of pathology and medicine at HMS, emphasized that this research marks vital progress toward creating the first highly accurate, single-step CDI diagnostic test. “The next steps for the research will combine this ultrasensitive and quantitative stool toxin test with other biomarkers to try to create a test that can determine who really has C difficile infection and who is most likely to have worse clinical outcomes.”

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