Question
Clostridium difficile
Answer
Clostridium difficile is an anaerobic, spore-forming, Gram-positive bacillus that is the principal cause of antibiotic-associated diarrhoea and pseudomembranous colitis.
Pathogenesis: broad-spectrum antibiotic therapy (classically clindamycin, cephalosporins, fluoroquinolones) disrupts normal protective gut flora, allowing C. difficile (acquired from the environment/hospital as spores, which resist normal disinfection) to colonize and overgrow the colon. Toxigenic strains produce Toxin A (enterotoxin, damages intestinal mucosa and recruits inflammatory cells) and Toxin B (cytotoxin, more potent, disrupts the actin cytoskeleton of colonic epithelial cells), together causing mucosal inflammation, necrosis, and the formation of characteristic yellowish adherent pseudomembranes seen on colonoscopy.
Clinical spectrum: ranges from mild self-limiting diarrhoea to severe pseudomembranous colitis with fever, abdominal pain, and (in severe cases) toxic megacolon and perforation.
Laboratory diagnosis: enzyme immunoassay (EIA) for Toxin A/B in stool; glutamate dehydrogenase (GDH) antigen test as a rapid screen; nucleic acid amplification test (PCR) for toxin genes — the current gold standard; cytotoxin assay on cell culture (classical reference method); colonoscopy showing pseudomembranes in severe disease.
Treatment: discontinuation of the offending antibiotic where possible; oral metronidazole or vancomycin (first-line agents); fidaxomicin for recurrent disease; faecal microbiota transplantation for refractory/recurrent cases.