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]

Exam Intelligence

  1. GC 099 (Antimicrobial Resistance) & GC 106 (Practical Issues in Antibiotic Use): C. difficile is the paradigm organism for antibiotic stewardship — exam questions frequently frame it as the consequence of inappropriate broad-spectrum antibiotic use [1]. The lecture emphasis is that clindamycin, fluoroquinolones, and third-generation cephalosporins are the highest-risk antibiotics for triggering CDI.

  2. GC 104 (Infection Outbreak / Infection Control): C. difficile is a key healthcare-associated infection requiring contact precautions, soap-and-water hand hygiene, and environmental decontamination with sporicidal agents (bleach) [1]. Alcohol gel inefficacy is a favourite MCQ discriminator.

  3. GC 102 (Fever After Chemotherapy / Immunocompromised Hosts): In the post-chemotherapy neutropenic patient with diarrhoea, C. difficile must be excluded as a cause — stool toxin assay is mandatory [1]. The 2021 SAQ Q12 (see below) directly tests organisms causing diarrhoea post-bone-marrow transplant, where C. difficile is a key answer.

  4. CFB WCS27 (Surgical Infection): pseudomembranous colitis and toxic megacolon are surgical emergencies; colectomy may be needed for fulminant C. difficile colitis [1].

  5. AOS Microbiology: C. difficile toxin detection algorithm (GDH screen → toxin EIA/PCR) is high-yield for diagnostic questions [2]. Emphasise that testing should only be done on unformed stool and test-of-cure is not recommended.

  6. GC 033 (Chronic Diarrhoea / IBD) and GC 142 (A Child with Loose Stool): C. difficile should be considered in the differential of chronic/relapsing diarrhoea especially in patients with recent antibiotic exposure or hospitalisation [1]. In paediatric settings, note that neonates/infants < 12 months can be asymptomatically colonised — testing is generally not recommended in this age group.

  • Alcohol hand-rub vs soap-and-water: The single most tested infection control point for C. difficile. Spores are resistant to alcohol. Always choose soap-and-water.
  • Metronidazole vs vancomycin: Older guidelines used oral metronidazole as first-line for mild CDI. Current IDSA/SHEA guidelines (and GC lecture framing) prefer oral vancomycin or fidaxomicin as first-line for all severities [1][2]. Metronidazole is now reserved as adjunctive IV therapy in fulminant disease.
  • NAAT positivity trap: PCR detects the toxin gene, not active toxin. A positive NAAT in a patient with formed stool = colonisation, not infection. This is a common wrong-answer attractor.
  • Pseudomembranous colitis on colonoscopy: Yellow-white adherent plaques that cannot be washed off. This is pathognomonic but not present in all CDI cases.
  • C. difficile vs C. perfringens: Both are Gram-positive anaerobic spore-forming bacilli. C. perfringens causes gas gangrene (alpha toxin/lecithinase) and a self-limiting food poisoning (enterotoxin). C. difficile causes antibiotic-associated diarrhoea/pseudomembranous colitis. The clinical scenario discriminates them.
  • Fecal microbiota transplantation (FMT): Reserved for multiply recurrent CDI (≥ 2–3 recurrences). This is increasingly tested as a "novel therapy" question.

2021 Fourth Summative SAQ Q12 [3]:

"A 40-year-old man had bone marrow transplant for chronic myeloid leukaemia. ... (b) On day 28 after neutrophil engraftment, he developed fever, impaired liver function test, persistent diarrhoea and chest X-ray infiltrates. The patient admitted that he did not take the antimicrobial prophylaxis which was prescribed. List [four] organisms which may account for his symptoms."

  • Correct answer (for diarrhoea component): Clostridioides difficile is a key answer for the persistent diarrhoea in a post-BMT patient (antibiotic exposure is universal in this setting). Other expected answers include CMV (colitis + hepatitis + pneumonitis), Aspergillus (CXR infiltrates), and Pneumocystis jirovecii (if co-trimoxazole prophylaxis not taken). The question tests recognition that CDI must be excluded in any post-chemotherapy/transplant patient with diarrhoea.

No other past paper questions in the indexed context directly and specifically test C. difficile as the primary organism. However, CDI is a plausible differential in several diarrhoea-related stems (e.g., 2019 Minicase Case 1 — traveller with diarrhoea, though enteric fever is the primary answer there).


[1] Lecture slides: GC 099 (Antimicrobial Resistance), GC 102 (Fever After Chemotherapy), GC 104 (Infection Outbreak/Infection Control), GC 106 (Practical Issues in Antibiotic Use), GC 033 (Chronic Diarrhoea/IBD), GC 142 (A Child with Loose Stool), CFB WCS27 (Surgical Infection) [2] AOS material: AOS - Microbio.pdf; Gen Clerk Anaes + Microbiology Summary.pdf [3] Past papers: 2021 Fourth Summative SAQ (2021 Fourth Summative SAQ.pdf), Q12

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