Core concept
- Toxin A (enterotoxin) and toxin B (cytotoxin) both glucosylate and inactivate Rho-family GTPases in colonic epithelial cells -> disrupts the actin cytoskeleton -> cell rounding, tight junction breakdown, apoptosis -> colitis with fluid secretion and inflammation (pseudomembrane formation in severe disease)
- Toxin B is the more essential virulence factor -- toxin-B-only strains still cause disease; toxin-A-only strains are far less pathogenic
- Disease results from disruption of normal colonic flora (usually antibiotic-associated) allowing C. difficile overgrowth and toxin production -- spores are the transmissible/resistant form, surviving alcohol hand gel and standard disinfection
Key detail
- Diagnosis: toxin EIA or PCR (NAAT) for toxin genes on symptomatic (diarrhoeal) stool only -- PCR detects the gene, not active toxin production, so a positive PCR in an asymptomatic patient reflects colonisation, not disease, and should not be treated
- First-line treatment (current guidance): oral fidaxomicin preferred over oral vancomycin for initial and recurrent episodes -- fidaxomicin reduces recurrence risk (narrower spectrum, less collateral flora disruption) though cure rates are similar
- Severe/fulminant disease (ileus, toxic megacolon, shock): oral vancomycin + IV metronidazole, surgical review for colectomy if deteriorating -- fidaxomicin not established in this setting
Clinical relevance
- Hand hygiene: soap and water, not alcohol gel -- spores are resistant to alcohol; contact precautions with dedicated equipment are required to prevent spread
- Trap: repeat-testing/re-treating a patient with persistent loose stool but no ongoing symptoms based on a positive PCR alone -- PCR positivity can persist after clinical cure and does not indicate treatment failure
- Recurrent CDI (within ~8 weeks of prior episode): fidaxomicin preferred, with faecal microbiota transplant considered after multiple recurrences -- restores colonic flora diversity directly
Correlations
- Antibiotic classes most associated with precipitating CDI: clindamycin (highest risk), fluoroquinolones, cephalosporins - see antibiotic class-specific adverse effects
- Same Rho-GTPase/cytoskeletal disruption mechanism theme (toxin-mediated cell rounding) parallels other bacterial exotoxin mechanisms, though the specific target differs from, e.g., diphtheria/pertussis toxins (ADP-ribosylation of different targets)
- PCR-vs-toxin-EIA distinction (gene detection vs active toxin) is a recurring theme in molecular diagnostics -- same principle as interpreting any NAAT result in the context of colonisation vs true infection
4 of 4 sections written · drafted 2026-09-13