Overview
Clostridioides difficile Infection
Topic Overview
Summary
Clostridioides difficile infection (CDI) is antibiotic-associated diarrhoea caused by toxin-producing C. difficile. It ranges from mild diarrhoea to life-threatening pseudomembranous colitis, toxic megacolon, and sepsis. Risk factors include antibiotic exposure, hospitalisation, age, and PPI use. Diagnosis is by stool toxin testing. Treatment depends on severity: oral vancomycin or fidaxomicin for non-severe; high-dose vancomycin ± IV metronidazole for severe/fulminant. Stop inciting antibiotics, implement infection control measures, and consider faecal microbiota transplant (FMT) for recurrent CDI.
Key Facts
- Cause: Toxin-producing C. difficile (toxins A and B)
- Risk factors: Antibiotics (especially clindamycin, cephalosporins, fluoroquinolones), hospitalisation, age, PPIs
- Diagnosis: Stool GDH + toxin EIA, or PCR
- Treatment: Oral vancomycin (first-line) or fidaxomicin
- Severe/fulminant: High-dose vancomycin + IV metronidazole; surgical consult
Clinical Pearls
Stop the inciting antibiotic if possible — this is as important as CDI treatment
Oral vancomycin is first-line (NOT IV — doesn't reach colon)
Fidaxomicin has lower recurrence rate but is more expensive
Why This Matters Clinically
CDI is common in hospital and community settings. Fulminant CDI has high mortality. Appropriate antibiotic stewardship and infection control prevent spread.
Visual Summary
Visual assets to be added:
- CDI severity classification
- Pseudomembranous colitis colonoscopy
- Two-step testing algorithm
- CDI treatment algorithm
Epidemiology
Incidence
- 20-30 per 100,000 population/year
- Most common healthcare-associated infection in some settings
- Community-acquired CDI increasing
Demographics
- Elderly (over 65)
- Hospitalised patients
- Nursing home residents
Risk Factors
| Factor | Notes |
|---|---|
| Antibiotic exposure | Main risk factor |
| High-risk antibiotics | Clindamycin, cephalosporins, fluoroquinolones |
| Hospitalisation | |
| Age over 65 | |
| PPI use | Controversial but linked |
| Immunocompromise | |
| GI surgery | |
| NG tube feeding |
Pathophysiology
Mechanism
- Antibiotic disrupts normal gut flora
- C. difficile (spores in environment) colonises colon
- Toxin production (toxin A and B)
- Toxins damage enterocytes → inflammation, fluid secretion
- Colitis, pseudomembranes
Toxins
- Toxin A: Enterotoxin
- Toxin B: Cytotoxin (more potent)
- Binary toxin (CDT): Associated with hypervirulent strains
Hypervirulent Strains
- Ribotype 027 (NAP1)
- Increased toxin production
- More severe disease
Clinical Presentation
Symptoms
Signs
Severity Classification
| Severity | Criteria |
|---|---|
| Non-severe | WCC under 15, creatinine under 1.5x baseline |
| Severe | WCC over 15 OR creatinine over 1.5x baseline |
| Fulminant | Hypotension, shock, ileus, megacolon, ICU admission |
Red Flags
| Finding | Significance |
|---|---|
| Toxic megacolon | Surgical emergency |
| Ileus (no diarrhoea) | May mask CDI |
| Peritonism | Perforation |
| Lactate elevated | Severe sepsis |
Watery diarrhoea (3+ loose stools/day)
Common presentation.
Abdominal cramping
Common presentation.
Fever
Common presentation.
Nausea
Common presentation.
Clinical Examination
General
- Fever
- Dehydration
- Tachycardia
Abdominal
- Tenderness
- Distension
- Reduced bowel sounds (ileus)
- Peritonism (perforation)
Investigations
Stool Testing
| Test | Purpose |
|---|---|
| GDH (glutamate dehydrogenase) | Screening; sensitive for C. diff |
| Toxin EIA | Confirms toxin production |
| PCR (toxin gene) | Sensitive; may detect colonisation |
Two-Step Algorithm:
- GDH positive → test for toxin
- GDH positive, toxin positive = CDI
- GDH positive, toxin negative, PCR positive = possible CDI or colonisation
Blood Tests
| Test | Finding |
|---|---|
| WCC | Often elevated (over 15 = severe) |
| Creatinine | Rising = severe |
| Lactate | If septic |
| Albumin | Low in severe |
Imaging
| Modality | Findings |
|---|---|
| Abdominal X-ray | Megacolon (transverse over 6cm) |
| CT abdomen | Colonic wall thickening, "accordion sign" |
Colonoscopy
- Pseudomembranes (yellowish plaques)
- Usually not needed; risk of perforation
Classification & Staging
By Severity
| Severity | Definition |
|---|---|
| Non-severe | WCC under 15, creatinine normal |
| Severe | WCC over 15 OR creatinine over 1.5x baseline |
| Fulminant | Shock, ileus, megacolon |
By Episode
- Initial episode
- Recurrence (within 8 weeks of successful treatment)
Management
General Measures
| Action | Details |
|---|---|
| Stop inciting antibiotic | If possible |
| Infection control | Isolation, contact precautions, hand washing with soap |
| Avoid antidiarrhoeal | Avoid loperamide (may increase toxin retention) |
| IV fluids | If dehydrated |
Antibiotic Treatment
Non-Severe:
| Agent | Dose |
|---|---|
| Oral vancomycin | 125mg QDS for 10 days |
| Or fidaxomicin | 200mg BD for 10 days (lower recurrence) |
Severe:
| Agent | Dose |
|---|---|
| Oral vancomycin | 125mg QDS for 10 days |
| Consider fidaxomicin | 200mg BD |
Fulminant:
| Agent | Dose |
|---|---|
| Oral/NG vancomycin | 500mg QDS |
| + IV metronidazole | 500mg TDS |
| + PR vancomycin | If ileus (100mL retention enema) |
| Surgical consult | Colectomy may be needed |
Recurrent CDI (2+ Episodes)
| Option | Notes |
|---|---|
| Fidaxomicin | Preferred for recurrence |
| Vancomycin taper | Prolonged taper/pulse regimen |
| FMT (faecal microbiota transplant) | Highly effective for recurrent CDI |
| Bezlotoxumab | Monoclonal antibody (reduces recurrence) |
Surgical Intervention
- Toxic megacolon, perforation, refractory shock
- Subtotal colectomy
Complications
GI
- Toxic megacolon
- Colonic perforation
- Ileus
Systemic
- Sepsis
- Multi-organ failure
- Death (3-15% mortality)
Recurrence
- 20-30% recurrence after first episode
- Higher after subsequent episodes
Prognosis & Outcomes
Prognosis
- Non-severe: Good with treatment
- Fulminant: Mortality 25-50%
Recurrence
- 20-30% after first episode
- FMT is highly effective for recurrent CDI
Evidence & Guidelines
Key Guidelines
- PHE/UKHSA Guidance on CDI
- IDSA/SHEA Clinical Practice Guidelines for CDI
Key Evidence
- Fidaxomicin reduces recurrence vs vancomycin
- FMT is highly effective for recurrent CDI
Patient & Family Information
What is C. diff?
C. diff is an infection of the bowel that causes diarrhoea. It often happens after taking antibiotics.
Symptoms
- Watery diarrhoea (frequent)
- Tummy pain
- Fever
Treatment
- Specific antibiotics (vancomycin by mouth)
- Good hand hygiene
- Isolation to prevent spread
Prevention
- Antibiotics only when needed
- Hand washing with soap and water (alcohol gel less effective)
Resources
References
Primary Guidelines
- McDonald LC, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update (IDSA/SHEA). Clin Infect Dis. 2018;66(7):e1-e48. PMID: 29462280
Key Reviews
- Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372(16):1539-1548. PMID: 25875259
- van Prehn J, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection. Clin Microbiol Infect. 2021;27(Suppl 2):S1-S21. PMID: 34678515