Key Facts

C. difficile infection (CDI) remains a major cause of morbidity and mortality in hospitalised patients. UK mandatory surveillance has driven significant reduction in healthcare-associated CDI through antibiotic stewardship and infection prevention measures.

Epidemiology

• UK: ~13,000 cases/year reported (declining due to improved stewardship)
• Accounts for 15–25% of antibiotic-associated diarrhoea
• Mortality: 1–5% overall; up to 25–30% in fulminant colitis
• 30-day mortality: ~15% in elderly hospitalised patients
• Community-acquired CDI increasing (~25% of cases)

Aetiology

• Clostridioides difficile: Gram-positive, anaerobic, spore-forming bacillus
• Produces toxin A (enterotoxin) and toxin B (cytotoxin) — cause mucosal damage
• Binary toxin (CDT): produced by hypervirulent ribotype 027
• Antibiotic exposure disrupts normal colonic microbiota → C. difficile colonisation → toxin production
• Spores: resistant to alcohol-based hand gels and standard cleaning — require sporicidal agents (bleach, hydrogen peroxide)

Pathophysiology

• Normal colonic flora provides colonisation resistance against C. difficile
• Antibiotics (especially broad-spectrum) disrupt this → spore germination → vegetative growth → toxin production
• Toxin A and B → disruption of tight junctions, cytoskeletal damage → inflammation, fluid secretion, mucosal necrosis
• Pseudomembrane formation: raised yellow-white plaques on colonic mucosa
• Severe colitis → toxic megacolon → perforation

Mild-Moderate CDI

• Watery diarrhoea (≥3 loose stools in 24 hours) — NOT bloody
• Lower abdominal cramping
• Low-grade fever
• Recent antibiotic history (onset typically 5–10 days after antibiotics but can be up to 8 weeks)

Severe CDI

• Profuse diarrhoea (>10 stools/day)
• Fever >38.5°C
• Raised WCC (>15 × 10⁹/L)
• Rising creatinine (>50% above baseline)
• Dehydration, electrolyte disturbance

Fulminant/Life-Threatening CDI

• Toxic megacolon: abdominal distension, absent bowel sounds, peritonism
• Ileus: may paradoxically have REDUCED diarrhoea
• Septic shock, multi-organ failure
• Lactate >2.2 mmol/L

Red Flags

• Abdominal distension with peritonism (toxic megacolon/perforation)
• WCC >15 or <1.5 × 10⁹/L
• Rising lactate or creatinine
• Ileus (reduced stool output may indicate worsening, not improvement)
• Temperature >38.5°C despite treatment
• Failure to improve after 48–72 hours of treatment

Bedside

• Stool sample: ONLY test loose/watery stools (Bristol type 5–7) — do NOT test formed stools
• Observations: temperature, HR, BP, NEWS2

Bloods

• FBC: leucocytosis (WCC >15 = marker of severity)
• U&Es: AKI, dehydration
• CRP: elevated
• Lactate: raised in severe/fulminant
• Albumin: low (poor prognostic marker)

Stool Tests

• Two-stage testing: GDH (glutamate dehydrogenase) screen → if positive, toxin EIA (enzyme immunoassay) for toxin A/B
• GDH+/Toxin+: confirmed CDI
• GDH+/Toxin–: may be carrier; consider clinical context and PCR if available
• NAAT/PCR: highly sensitive but may detect carriers (positive for toxin gene, not necessarily active toxin)

Imaging

• AXR: if toxic megacolon suspected (colonic dilation >6cm)
• CT abdomen: colonic wall thickening (accordion sign), pericolonic fat stranding, ascites; free air if perforation

Non-pharmacological

• Stop precipitating antibiotics if possible (or switch to lower-risk agents)
• Isolation: single room with dedicated bathroom; contact precautions
• Hand washing with soap and water: alcohol gel does NOT kill spores
• Environmental cleaning: sporicidal agents (bleach-based)
• Review PPI: stop if not essential (associated with CDI recurrence)
• Avoid antidiarrhoeal agents (loperamide): risk of toxic megacolon

Pharmacological

First episode (NICE NG199):

• Oral vancomycin 125mg QDS for 10 days (first-line)
• OR fidaxomicin 200mg BD for 10 days (if high risk of recurrence: >65, severe, concurrent antibiotics)
• Metronidazole 400mg TDS oral for 10 days: only if vancomycin/fidaxomicin unavailable

First recurrence:

• Fidaxomicin 200mg BD for 10 days (preferred — lower recurrence rate)
• OR vancomycin tapering/pulsed regimen: 125mg QDS 14 days → 125mg BD 7 days → 125mg OD 7 days → 125mg every 2–3 days for 2–4 weeks

Second or subsequent recurrence:

• Faecal microbiota transplantation (FMT): ~90% effective; recommended by NICE for ≥2 recurrences
• Fidaxomicin or vancomycin taper as bridge to FMT

Severe/fulminant CDI:

• Oral vancomycin 500mg QDS (higher dose)
• ± IV metronidazole 500mg TDS if ileus (oral vancomycin may not reach colon)
• ± Rectal vancomycin 500mg in 100ml NaCl QDS (via rectal tube) if complete ileus

MODIFY I/II trials:

• Fidaxomicin non-inferior to vancomycin for initial cure; superior for recurrence prevention (~13% vs ~27%)

Surgical/Interventional

• Subtotal colectomy: for toxic megacolon, perforation, or refractory fulminant CDI
• Loop ileostomy with colonic vancomycin lavage: emerging alternative to colectomy

Referral Criteria

• Gastroenterology: severe CDI, recurrent CDI for FMT
• Surgery: toxic megacolon, perforation, failure to improve on maximum medical therapy
• Infection prevention team: all cases (mandatory reporting)

• Mild-moderate CDI: >90% cure rate with oral vancomycin
• Recurrence rate: ~20–25% after first episode; ~40–60% after second episode
• Fidaxomicin: reduces recurrence by ~50% compared to vancomycin
• FMT: ~90% cure for recurrent CDI
• Severe CDI: 15–20% mortality
• Fulminant CDI/toxic megacolon: mortality 30–50%
• 30-day all-cause mortality in hospitalised CDI: ~15% (elderly)
• Long-term: most patients recover fully; some develop post-infectious IBS
• UK mandatory surveillance has contributed to >50% reduction in healthcare-associated CDI since 2007

CDI Severity Classification

High-Risk Antibiotics for CDI (4Cs)