Gram-positiveBacilliSpore-forming

Clostridioides difficile

Anaerobic, Gram-positive, spore-forming, toxin-producing bacillus that is the leading cause of healthcare-associated antibiotic-related diarrhea and pseudomembranous colitis.

Organism Card

DomainMust know
Identity
  • Gram-positive, anaerobic, spore-forming bacillus [1][2]
  • Formerly Clostridium difficile; reclassified as Clostridioides difficile
  • Spores are environmentally resistant → persist on surfaces, resist alcohol hand-rub [1][2]
Lab discriminator
  • Subterminal spores on Gram stain (vs terminal spores in C. tetani) [2]
  • Grows on cycloserine-cefoxitin-fructose agar (CCFA) under anaerobic conditions
  • Horse-barn / "barnyard" odour on culture
  • Distinguished from other clostridia by toxin production profile (TcdA/TcdB)
Reservoir / transmission
  • Healthcare-associated infection: transmitted by spores via fecal-oral route in hospital environment [1][2]
  • Spores survive on environmental surfaces (bed rails, commodes, stethoscopes)
  • Contact precautions mandatory; hand hygiene with soap and water (alcohol gel does NOT kill spores) [1][2]
  • Endogenous colonisation of gut (carrier state) can be source after antibiotic disruption of normal flora
Key virulence
  • Toxin A (TcdA) = enterotoxin → fluid secretion and mucosal inflammation [2]
  • Toxin B (TcdB) = cytotoxin → epithelial cell damage; more potent [2]
  • Both toxins glucosylate Rho-family GTPases → cytoskeletal disruption, apoptosis
  • Binary toxin (CDT) in hypervirulent ribotype 027 → increased severity, higher relapse [2]
  • Spore formation = key to environmental persistence and transmission
Clinical syndromes
  • Antibiotic-associated diarrhoea (most common identifiable cause) [1][2]
  • Pseudomembranous colitis: yellow-white raised plaques on colonoscopy [1][2]
  • Toxic megacolon, colonic perforation, septic shock (severe/fulminant disease)
  • Classic scenario: elderly hospitalised patient on broad-spectrum antibiotics (clindamycin, fluoroquinolones, cephalosporins, amoxicillin-clavulanate) developing watery diarrhoea ± fever ± leukocytosis [1][2]
  • Risk factors: age > 65, prolonged hospitalisation, PPI use, immunosuppression
Diagnosis
  • Stool toxin assay: GDH (glutamate dehydrogenase) screen + toxin A/B EIA or NAAT (PCR for toxin gene) [1][2]
  • Two-step algorithm common: GDH screen → if positive, confirm with toxin EIA or PCR
  • Do NOT test formed stool; only test diarrhoeal (loose/watery) specimens [2]
  • Do NOT do test-of-cure (repeat testing after treatment is unreliable) [2]
  • Colonoscopy: pseudomembranes are pathognomonic but not always performed
  • Pitfall: NAAT detects gene not active toxin → can be positive in asymptomatic carriers
Treatment
  • Step 1: discontinue the offending antibiotic if possible [1][2]
  • Non-severe first episode: oral vancomycin 125 mg QDS × 10 days (preferred) or fidaxomicin [1][2]
  • Severe disease (WCC ≥ 15 × 10⁹/L, Cr ≥ 1.5 mg/dL): oral vancomycin ± IV metronidazole [2]
  • Fulminant (toxic megacolon / ileus): high-dose oral vancomycin + IV metronidazole ± rectal vancomycin; surgical consult for colectomy [2]
  • Metronidazole is no longer first-line for initial episode (higher recurrence rate vs vancomycin) [1][2]
  • Recurrent CDI: fidaxomicin preferred; fecal microbiota transplantation (FMT) for multiple recurrences [2]
  • Avoid anti-motility agents (loperamide) → risk of toxic megacolon
Prevention
  • Contact precautions + single room isolation for symptomatic patients [1][2]
  • Hand washing with soap and water (NOT alcohol-based hand rub) [1][2]
  • Environmental disinfection with sporicidal agents (sodium hypochlorite / bleach) [1][2]
  • Antibiotic stewardship: restrict unnecessary broad-spectrum antibiotics [1][2]
  • Notification: reportable as healthcare-associated infection in most hospital infection control frameworks
  • No vaccine currently available for routine use
Classic traps
  • Alcohol hand-rub ineffective against C. difficile spores — a classic MCQ trap [1][2]
  • Don't confuse with Clostridium perfringens food poisoning (short incubation, self-limiting, no pseudomembranes)
  • Pseudomembranous colitis ≠ always C. difficile (rarely: ischaemic colitis, other infections), but in exam context CDI is the answer
  • NAAT-positive without diarrhoea = colonisation, not disease → do not treat
  • Post-treatment: do NOT repeat stool testing to confirm cure
  • In immunocompromised / post-chemotherapy diarrhoea, CDI must be excluded alongside neutropenic enterocolitis [1][2]

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