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
Study aid only. These notes are written with the help of AI. Not for guiding clinical decisions.