Levels of toxins in stool correlate directly with severity of Clostridioides Difficult infection

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

C diff is very common in and outside healthcare settings, but healthy people can carry the bacteria without illness or symptoms. There are several tests that can detect the presence of Diff C, such as the nucleic acid amplification test (NAAT), but these do not distinguish between infection and colonization.

Researchers at Beth Israel Deaconess Medical Center (BIDMC) set out to develop a highly sensitive and quantitative immunotoxin test. The test was based on single-DNA chip technology and qualified stool concentrations of ≥20 pg / mL for toxin A or B were positive.

Until this study, published in Clinical infectious diseases, no research had established a quantitative relationship between the concentration of bacteria and the severity of the disease.

In the study, investigators recruited 615 adults hospitalized for ICD at BIDMC or Texas Medical Center in Houston. The average age of the participants was 68 years old. All patients had acute diarrhea, tested positive (NAAT) and had started treatment with ICD. Investigators followed patients for 40 days after the onset of CDI, collecting stool samples and monitoring symptoms and recovery.

The results showed what was suspected but never confirmed: individuals with severe baseline disease had higher relative concentrations of A + B toxins in the stool. 19 subjects (3.1%) had a severe outcome from CDI and had a higher median toxin A + B value [14,303 pg/mL (IQR 416.0, 141,967)] that the subjects in whom the CDI only contributed to the result [163.2 pg/mL (0.0, 8423.3)], subjects with severe results 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 results had significantly more detectable toxin (94.7%) than the other patients (60.5-66.1%) (P = 0.02 ).

Detection and concentration of the toxin in the stool have consistently indicated serious findings and recurrence attributable to CDI. Patients with recurrent CDI had higher toxin A + B [2266.8 pg/mL(188.8, 29411)] than those without recurrence [154.0 pg/mL(0.0, 5864.3)](P

Senior Author / Correspondent Nira R. Pollock, MD, PhD, Division of Infectious Diseases at BIDMC, Associate Medical Director of the Infectious Disease Diagnostic Laboratory at Boston Children’s Hospital and Associate Professor of Pathology and Medicine at HMS, a pointed out that this research marks vital progress towards creating the first highly accurate one-step CDI diagnostic test. “The next steps in the research will combine this highly sensitive, quantitative fecal toxin test with other biomarkers to try to create a test that can determine who really has it’s hard infection and who is most likely to have the worst clinical outcome.

About Hector Hedgepeth

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