Clostridioides difficile (C. diff) is the leading cause of gastroenteritis-associated death in North America. While most people affected will fully recover, new research from Vancouver Coastal Health Research Institute scientist Dr Theodore Steiner explores how to identify the roughly 25% to 35% of patients who will experience recurrent or severe infection.
The Centers for Disease Control and Prevention defines C. diff as a significant health concern because it can cause life-threatening diarrhea and inflammation of the colon. At greatest risk of becoming dangerously ill or dying due to the infection are people ages 65 and older who take antibiotics, along with individuals with a prior C. diff infection and people who are hospitalized or living in long-term care homes. Young and middle-aged adults can also be plagued by recurrent infections that cause life-altering diarrhea, abdominal cramps, and potential hospitalizations.
Dr Steiner is a professor and the head of the Division of Infectious Diseases, an associate member in the Department of Microbiology and Immunology at the University of British Columbia, and a researcher in the Immunity and Infection Research Centre. His research, published in Gastroenterology, found that CD4+ T-cell immune response to the C. diff toxins A and B was higher among patients who experienced recurrent or more severe C. diff infection compared with individuals with their first episode of C. diff. Part of the body’s immune system, CD4+ T-cells are specialists in gut-related infections. They can help fight C. diff by recruiting cytokine molecules to signal the immune system to attack the infection and to produce antibodies that neutralize the toxins, preventing them from damaging cells. A potential biomarker, the greater presence of CD4+ T-cell response to the C. diff A and B toxins could help clinicians identify which patients are more likely to recover through first-line antibiotic treatments, and which may require additional interventions.
Fecal transplantation as alternative therapy for treatment-resistant C. diff
C. diff infection occurs through ingesting the pathogen, which is found in water, soil, food, and human and animal feces. Once infection occurs, the first-line treatment is a course of antibiotics, such as vancomycin or metronidazole. These medications work by destroying bacteria in the intestines. However, they do not block the C. diff A and B pathogenic toxins that cause damaging inflammation. They also destroy healthy gut bacteria, which can create a more favorable environment for C. diff recurrence or reinfection. Patients who do not respond to at least two rounds of antibiotics may be prescribed fecal microbiota transplantation (FMT), a well-established procedure in which stool from a healthy donor is transplanted into the patient’s gastrointestinal tract.
In another study published in Gastroenterology in January 2021, Steiner found that this second-line treatment for recurrent and severe C. diff improved Th17 counts—a type of CD4+ T-cell—as well as antibodies to C. diff toxins A and B, all of which supported the greater balance of healthy gut flora essential to disease recovery.
Studies have shown a 90% global effectiveness of FMT on this patient cohort, according to Steiner. While more involved than antibiotic treatments, the Health Canada–approved intervention may be the best option for many people with a treatment-resistant infection.
Steiner is currently recruiting adults ages 18 and older with a first instance of C. diff infection for his new onset C. diff study. For more information, contact study coordinator Laura Oliveira at firstname.lastname@example.org.
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