Clostridioides difficile, or C. diff, is a bacterium that causes severe gut issues, primarily antibiotic-associated diarrhea. Infections range from mild discomfort to severe conditions like pseudomembranous colitis. C. diff is not a single entity, but comprises various “strains” with differing characteristics. These distinctions are important because they influence how the bacterium causes illness and how infections are managed.
What Defines a C. difficile Strain
C. difficile strains are differentiated by their genetic makeup, which influences their biological behaviors. Genetic variations contribute to differences in toxin production, influencing virulence. Many strains produce Toxin A (TcdA) and Toxin B (TcdB), which are major virulence factors. Some strains also produce binary toxin. These toxin genes are located within a specific region of the bacterial chromosome called the pathogenicity locus (PaLoc).
Differences in PaLoc genes can alter the toxins a strain produces or their quantity. Strains also vary in their ability to form spores. Spores are dormant, highly resistant structures allowing bacteria to survive harsh conditions outside a host. These genetic differences contribute to varied virulence among C. difficile strains.
How C. difficile Strains Cause Illness
C. difficile infection begins when a person ingests spores of a toxigenic strain. Spores can survive stomach acid and persist in the environment. Once in the small intestine, they germinate into active, vegetative cells.
Vegetative C. difficile cells colonize the large intestine, especially when the normal gut microbiota has been disrupted, often by antibiotic use. This disruption allows C. diff to multiply without competition from beneficial bacteria. As the bacteria proliferate, they produce toxins, primarily Toxin A and Toxin B, released into the intestinal lining. These toxins damage intestinal cells, leading to inflammation, fluid secretion, and symptoms such as diarrhea and abdominal pain.
Identifying and Managing Infections Caused by Specific Strains
Diagnosis
Diagnosis involves laboratory tests on stool samples. Common approaches include detecting the C. difficile glutamate dehydrogenase (GDH) antigen, indicating the bacterium’s presence, and immunoassays for Toxin A and/or Toxin B.
PCR tests are also widely used. These molecular tests are highly sensitive and identify genes associated with toxin production, indicating a toxigenic strain. However, a positive PCR test alone does not always mean active disease, as it can detect asymptomatic carriers.
Treatment and Prevention
Treatment often begins by stopping antibiotics that disrupted gut flora, as this can resolve milder infections. If symptoms persist or are severe, specific antibiotics like vancomycin or fidaxomicin are prescribed. For recurrent infections, fecal microbiota transplantation (FMT) is effective. This procedure transfers stool from a healthy donor into the patient’s colon to restore a balanced gut microbiome, suppressing C. difficile overgrowth.
Prevention focuses on reducing transmission and limiting factors that promote C. difficile growth. Hand hygiene with soap and water is recommended, as alcohol-based sanitizers are not effective against C. diff spores. Environmental disinfection with sporicidal agents in healthcare settings helps control spread. Antibiotic stewardship programs, promoting appropriate antibiotic use, minimize gut microbiota disruption and reduce C. difficile risk.