About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Clostridioides (formerly Clostridium) difficile produces toxins A and B that damage colonic mucosa. Overgrowth occurs when normal gut flora is disrupted by antibiotics
- Highest-risk antibiotics: 4 Cs — Clindamycin, Co-amoxiclav, Cephalosporins, Ciprofloxacin (and other fluoroquinolones). Also PPIs increase risk
- Diagnosis: stool sample for C. difficile toxin (GDH screening then toxin EIA or NAAT). Do NOT test formed stools — only test loose/watery stool (Bristol type 5-7)
- First episode mild-moderate: oral vancomycin 125 mg QDS for 10 days (first-line) or fidaxomicin 200 mg BD for 10 days (lower recurrence rate)
- STOP the causative antibiotic if possible. Isolate patient, infection control measures (hand washing with soap and water — alcohol gel does NOT kill spores)
Overview
Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infectious diarrhoea. C. difficile is a Gram-positive, spore-forming, obligate anaerobe. Pathogenic strains produce toxins A (enterotoxin) and B (cytotoxin) that cause mucosal inflammation and damage. CDI occurs when the normal colonic microbiome is disrupted — most commonly by antibiotic use — allowing C. difficile to proliferate and produce toxin. The spectrum ranges from mild diarrhoea to severe pseudomembranous colitis, toxic megacolon, and death.
Epidemiology
CDI causes approximately 13,000 cases per year in England. Incidence has declined significantly since 2007 due to antimicrobial stewardship and improved infection control. Risk factors include: recent antibiotic use (strongest risk factor), age >65, hospitalisation, PPI use, immunosuppression, and IBD. The hypervirulent strain ribotype 027 (NAP1/BI) is associated with more severe disease and higher mortality. CDI recurrence occurs in approximately 20-25% after initial treatment.
Clinical Features
Symptoms
Watery diarrhoea (≥3 loose/liquid stools in 24 hours) — often profuse and offensive
Abdominal pain and cramping
Fever
Nausea and anorexia
Abdominal distension with absent bowel sounds (toxic megacolon)
Bloody diarrhoea (suggests severe colitis)
Signs
Abdominal tenderness
Fever >38.5°C (suggests severe disease)
Signs of dehydration
Abdominal distension and tympany (toxic megacolon)
Peritonism (perforation)
Investigations
First-line
Stool sample for C. difficileTwo-stage testing: (1) GDH antigen (screening — high sensitivity) → if positive: (2) Toxin EIA or NAAT for toxin genes. Only test loose/watery stools (Bristol 5-7). Do NOT test formed stools or test of cure
FBC, U&Es, CRP, albuminRaised WCC (often markedly elevated — WCC >15 is a severity marker), AKI, raised CRP, low albumin
Second-line
Abdominal X-rayIf severe: look for colonic dilatation >6 cm (toxic megacolon), mucosal oedema (thumbprinting)
CT abdomenColonic wall thickening, pericolic stranding, ascites. Toxic megacolon, perforation
Specialist
Flexible sigmoidoscopyMay show pseudomembranes (yellowish-white plaques on inflamed mucosa) — pathognomonic but not required for diagnosis in most cases
1
Immediate actions
- STOP the causative antibiotic if clinically possible
- Isolate patient in side room with dedicated toilet/commode
- Hand hygiene: SOAP AND WATER — alcohol hand gel does NOT kill C. difficile spores
- Avoid PPIs and anti-motility agents (loperamide) — may worsen disease
2
First episode — treatment
- Mild-moderate: oral vancomycin 125 mg QDS for 10 days (first-line)
- Alternative: fidaxomicin 200 mg BD for 10 days (similar efficacy, LOWER recurrence rate — preferred if recurrence risk is high)
- If oral treatment not possible: IV metronidazole 500 mg TDS (inferior to oral vancomycin but may be the only option in severe ileus)
3
Severe or life-threatening CDI
- Markers of severity: WCC >15, rising creatinine, temperature >38.5°C, albumin <25
- Oral vancomycin 125 mg QDS ± IV metronidazole 500 mg TDS
- Life-threatening (toxic megacolon, ileus, colonic perforation): urgent surgical review for colectomy. Consider vancomycin enemas if oral route compromised
4
Recurrent CDI (≥2 episodes)
- First recurrence: fidaxomicin 200 mg BD for 10 days (preferred) or vancomycin tapering/pulsed regimen
- Multiple recurrences: consider faecal microbiota transplant (FMT) — restores normal colonic microbiome. NICE-approved for recurrent CDI after ≥2 recurrences
- Bezlotoxumab (monoclonal antibody against toxin B) — reduces recurrence when given with standard antibiotics
Complications
- Toxic megacolon: Colonic dilatation >6 cm with systemic toxicity — risk of perforation. Surgical emergency
- Colonic perforation: Peritonitis, septic shock — high mortality
- Recurrence: 20-25% after first episode; higher with subsequent episodes. FMT can break the cycle
- Prolonged hospitalisation: CDI significantly increases length of stay and healthcare costs
UKMLA Exam Tips
- 1The 4 Cs of high-risk antibiotics: Clindamycin, Co-amoxiclav, Cephalosporins, Ciprofloxacin
- 2Oral VANCOMYCIN (not IV) is first-line for CDI — oral vancomycin is NOT absorbed so acts locally in the gut
- 3IV vancomycin does NOT treat CDI (does not reach the colonic lumen). IV metronidazole is the IV option (it is excreted into bile)
- 4Alcohol hand gel does NOT kill C. difficile spores — use SOAP AND WATER
- 5Do NOT send test of cure (repeat stool sample after treatment) — toxin can persist for weeks after clinical resolution
- 6Faecal microbiota transplant (FMT) for ≥2 recurrences — highly effective (>90% success rate)
- 7WCC >15 + raised creatinine + fever = markers of SEVERE CDI
practicetest your knowledge on c. difficileApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — infectious diseases and beyond.
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