In a new publication appearing in the journal Clinical Infectious Diseases, researcher physicians at Beth Israel Deaconess Medical Center (BIDMC), Boston, used a novel, highly sensitive test to measure the amount of toxin produced by the bacterium Clostridioides difficile (also known as C. difficile or “C. diff.”) in the stool of patients with suspected infections.

The team followed the patients—who were hospitalized at BIDMC and at Texas Medical Center in Houston—for 40 days after the onset of infection. The team found that the concentration of C. difficile toxins in the stool was linked to how sick patients were at the time of diagnosis and was also associated with adverse outcomes, including the risk of the infection returning after treatment.

“Disease-causing C. difficile strains produce toxins that directly damage the tissues of the large intestine, leading to the symptoms of C. difficile infection, including severe diarrhea, nausea, and stomach pain,” says first author Carolyn D. Alonso, MD, director of the Transplant and Immunocompromised Host Program in the Division of Infectious Diseases at BIDMC and assistant professor of medicine at Harvard Medical School (HMS). “While prior studies had shown a possible association between stool toxin levels and clinical outcomes, this study was the first of its kind to convincingly demonstrate that the concentration of C. difficile toxins influences disease severity.”

C. difficile is estimated to cause almost half a million infections per year, according to BIDMC. Most often affecting patients who are older or have weakened immune systems, C. difficile infections can cause diarrhea and inflammation of the large intestine. Infections are especially common among hospitalized patients and in patients who have recently completed a course of antibiotics.

“This research lays the foundation for developing a highly accurate, single-step test to better diagnose C. difficile infection and predict clinical outcomes,” says senior/corresponding author Nira R. Pollock, MD, PhD, also of the Division of Infectious Diseases at BIDMC, associate medical director of the Infectious Diseases Diagnostic Laboratory at Boston Children’s Hospital, and associate professor of pathology and medicine at HMS. “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.”

While several tests can detect the presence of C. difficile, healthy people can harbor the bacterium without becoming ill. A quantitative relationship between C. difficile and disease severity had not been clearly established.

“It is well-recognized that C. difficile-associated diarrhea and colitis are caused by toxins A and B,” says co-lead author Ciarán P Kelly, MD, medical director of the Celiac Center at BIDMC and professor of medicine at HMS. “However, this study clearly shows that toxin quantities are associated with baseline disease severity as well as negative outcomes such as need for admission to the ICU and/or death. Hence, measuring toxin concentrations in stool can help physicians to predict the likely course of the illness and plan their management steps accordingly.”

Co-authors include Kaitlyn Daugherty, Christine Cuddemi, Javier Villafuerte-Gálvez, Nicole C. White, Xinhua Chen, Hua Xu, Rebecca Sprague and Caitlin Barrett of BIDMC; Kevin W. Garey and Anne J Gonzales-Luna of University of Houston College of Pharmacy; David Williams of Boston Children’s Hospital; and Mark Miller, Agnès Foussadier, Aude Lantz, and Alice Banz of bioMérieux.

This study was funded by a grant from the National Institute of Allergy and Infectious Diseases as well as National Institute of Health Loan Repayment Funding. Simoa assays were provided as an in-kind service by bioMérieux.

Alonso has received grant support from Merck. Kelly has acted as a paid consultant to Artugen, Facile Therapeutics, Ferring, First Light Biosciences, Finch, Janssen (J&J), Matrivax, Merck, Seres, Pfizer, and Vedanta. Please see the publication for a complete list of financial disclosures.