Overview
Clostridioides difficile Infection (CDI)
1. Clinical Overview
Summary
Clostridioides difficile (Formerly Clostridium difficile) Infection (CDI) is a Toxin-Mediated Infection of the Colon causing Antibiotic-Associated Diarrhoea and Colitis, ranging from mild diarrhoea to Life-Threatening Fulminant Colitis, Toxic Megacolon, and Death. CDI is the Most Common Cause of Healthcare-Associated Infectious Diarrhoea in developed countries. The primary risk factor is Recent Antibiotic Exposure (Disrupts normal gut flora, Allowing C. difficile spores to germinate and proliferate). Other risk factors include Older Age (>65), Hospitalisation, PPI Use, and Immunocompromise. Diagnosis is by Stool Testing (GDH/Toxin EIA or PCR). Treatment is based on severity: Oral Vancomycin or Fidaxomicin for initial episodes (Metronidazole for mild if Vancomycin unavailable). Recurrent CDI is a major problem (~25% recur), with Fecal Microbiota Transplantation (FMT) highly effective for multiple recurrences. Infection Control measures (Hand Washing with Soap and Water, Isolation) are critical. [1,2,3]
Clinical Pearls
"Stop Unnecessary Antibiotics": First and most important step. The inciting antibiotic and any other unnecessary antibiotics.
"Vancomycin Oral, NOT IV for Gut Infection": Oral Vancomycin treats the colon. IV Vancomycin does not reach the gut.
"Alcohol Gel Does NOT Kill C. diff Spores": Use Soap and Water for hand hygiene.
"Recurrent CDI → Consider FMT": Fecal microbiota transplant is highly effective for recurrent CDI.
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Incidence | Major healthcare burden. ~500,000 cases/year in US. Mandatory reporting in UK. |
| Setting | Primarily Healthcare-Associated (Hospital, Nursing home). Increasing community-acquired cases. |
| Mortality | ~5% overall. ~15-20% in severe disease. |
Risk Factors
| Risk Factor | Notes |
|---|---|
| Antibiotic Exposure | Major risk. Any antibiotic. Highest risk: Clindamycin, Fluoroquinolones, Cephalosporins, Carbapenems, Penicillins. |
| Age >65 Years | |
| Hospitalisation / Healthcare Exposure | |
| Proton Pump Inhibitors (PPIs) | Reduce gastric acid barrier. |
| Immunocompromise | Chemotherapy, Organ transplant, IBD. |
| Previous CDI | High recurrence risk. |
| Comorbidities | Renal disease, Inflammatory bowel disease. |
3. Pathophysiology
Organism
| Feature | Notes |
|---|---|
| Clostridioides difficile | Gram-positive, Anaerobic, Spore-forming bacillus. |
| Spores | Resistant to heat, Drying, Alcohol. Persist in environment. Transmitted via faecal-oral route. |
| Toxins | Pathogenicity due to toxin production (Toxigenic strains). |
| - Toxin A (TcdA) | Enterotoxin. Causes fluid secretion and inflammation. |
| - Toxin B (TcdB) | Cytotoxin. Causes epithelial damage. Present in all pathogenic strains. |
| Hypervirulent Strain | NAP1/BI/027 (Ribotype 027). Produces more toxin. Severe disease. |
Mechanism
- Antibiotic Disruption of Gut Microbiota: Normal commensal bacteria suppressed.
- Spore Exposure: Ingestion of C. difficile spores (Environmental contamination, Healthcare worker hands).
- Germination: Spores germinate in colon (Bile acids altered by dysbiosis).
- Vegetative Growth and Toxin Production: Toxins A and B released.
- Mucosal Damage: Toxins bind to colonic epithelium → Cytoskeletal disruption, Inflammation, Cell death.
- Pseudomembrane Formation: Characteristic yellow-white plaques (Severe cases) composed of fibrin, Inflammatory cells, Debris.
- Clinical Disease: Diarrhoea, Colitis, Systemic inflammation.
4. Clinical Presentation
Spectrum of Disease
| Severity | Features |
|---|---|
| Non-Severe (Mild-Moderate) | Watery diarrhoea (≥3 loose stools/24h). Abdominal cramping. Low-grade fever. WCC less than 15,000. Creatinine less than 1.5x baseline. |
| Severe | Profuse diarrhoea. WCC ≥15,000. Creatinine ≥1.5x baseline. Significant abdominal pain/Tenderness. Albumin less than 30 g/L. |
| Fulminant / Life-Threatening | Hypotension. Septic shock. Ileus (Diarrhoea may decrease). Toxic megacolon. Peritonitis. Lactate >2.2. Organ failure. |
Symptoms
| Symptom | Notes |
|---|---|
| Watery Diarrhoea | Frequent. Foul-smelling. Sometimes mucoid or bloody. |
| Abdominal Cramping / Pain | Lower quadrants. |
| Fever | |
| Nausea | |
| Anorexia | |
| Dehydration |
Examination Findings
| Finding | Notes |
|---|---|
| Dehydration | Tachycardia. Hypotension. Dry mucous membranes. |
| Abdominal Tenderness | Diffuse. |
| Distension | If ileus/Toxic megacolon. |
| Peritonism | If perforation. |
| Reduced Bowel Sounds | Ileus. |
5. Investigations
Diagnosis
| Test | Notes |
|---|---|
| Stool Sample | For CDI testing. Only test Diarrhoeal Stool (Unformed, Conforms to container). Do NOT test formed stool. |
| GDH (Glutamate Dehydrogenase) Antigen | Screening. Highly sensitive. Detects all C. diff (Toxigenic and Non-toxigenic). |
| Toxin EIA (A & B) | Specific for toxigenic strains. Less sensitive than PCR. |
| PCR / NAAT (Nucleic Acid Amplification) | Detects toxin genes (tcdA, tcdB). Highly sensitive. May detect colonisation. |
| Two-Step Algorithm (Common) | GDH + Toxin EIA. If discordant → PCR. |
Interpretation: GDH+ / Toxin+ = CDI. GDH- / Toxin- = CDI unlikely. GDH+ / Toxin- = May be carrier or false negative toxin → Consider clinical picture or PCR.
Laboratory
| Test | Findings |
|---|---|
| FBC | Leucocytosis (WCC ≥15,000 in severe). Very high WCC (>30,000) = Poor prognosis. |
| U&Es / Creatinine | Elevated Creatinine (Dehydration, AKI). ≥1.5x baseline = Severe. |
| Albumin | Low (less than 30 g/L) = Severity marker. |
| Lactate | Elevated (>2.2 mmol/L) = Fulminant. |
| CRP | Elevated. |
Imaging
| Modality | Notes |
|---|---|
| CT Abdomen | Indicated if severe/Fulminant, Toxic megacolon suspected, Or diagnostic uncertainty. Findings: Colonic wall thickening ("Accordion sign" or "Thumbprinting"), Pericolonic fat stranding, Ascites, Megacolon (>6cm). |
| Abdominal X-Ray | May show megacolon. |
Endoscopy
| Notes |
|---|
| Generally NOT needed for diagnosis (Stool tests sufficient). |
| Colonoscopy/Sigmoidoscopy reserved for: Atypical presentation, Ileus (No stool sample), Need to exclude other pathology. |
| Finding: Pseudomembranes (Yellow-white plaques). Highly suggestive but not always present. |
6. Management
Management Algorithm
CDI CONFIRMED (Positive Stool Test + Clinical Diarrhoea)
↓
INITIAL STEPS (FOR ALL)
┌──────────────────────────────────────────────────────────┐
│ **STOP INCITING ANTIBIOTIC(S)** if possible │
│ **REVIEW ALL ANTIBIOTICS** – Stop any unnecessary │
│ **STOP PPIs** if possible (Review need) │
│ **SUPPORTIVE CARE**: IV Fluids, Electrolyte correction │
│ **INFECTION CONTROL**: │
│ - Isolate patient (Side room, Contact precautions) │
│ - **Soap and Water Hand Hygiene** (Alcohol gel does │
│ NOT kill spores) │
│ - Gloves and Aprons │
│ - Environmental cleaning (Sporicidal agents) │
│ **AVOID ANTI-MOTILITY AGENTS** (Loperamide) – Risk of │
│ toxic megacolon │
└──────────────────────────────────────────────────────────┘
↓
ASSESS SEVERITY
┌────────────────┬────────────────┬────────────────┐
NON-SEVERE SEVERE FULMINANT
(WCC less than 15, Cr normal) (WCC ≥15 or (Shock, Ileus,
Cr ≥1.5x) Megacolon, Lactate↑)
↓ ↓ ↓
TREATMENT
┌──────────────────────────────────────────────────────────┐
│ **INITIAL EPISODE (Non-Severe)** │
│ - **Fidaxomicin 200mg BD PO for 10 days** (Preferred – │
│ Lower recurrence) OR │
│ - **Vancomycin 125mg QDS PO for 10 days** │
│ - Metronidazole 400-500mg TDS PO for 10 days │
│ (Alternative if Vanc/Fidax unavailable) │
│ │
│ **INITIAL EPISODE (Severe)** │
│ - **Vancomycin 125mg QDS PO** (Can increase to 500mg │
│ QDS) OR │
│ - **Fidaxomicin 200mg BD PO** │
│ - Duration: 10-14 days │
│ │
│ **FULMINANT** │
│ - **Vancomycin 500mg QDS PO** + │
│ - **Vancomycin 500mg QDS PR** (Rectal instillation if │
│ ileus) + │
│ - **IV Metronidazole 500mg TDS** (Reaches colon via │
│ biliary excretion) │
│ - **ICU care**: Fluids, Vasopressors │
│ - **URGENT SURGICAL CONSULT**: Colectomy may be │
│ life-saving (Subtotal colectomy ± ileostomy) │
└──────────────────────────────────────────────────────────┘
↓
RECURRENT CDI
┌──────────────────────────────────────────────────────────┐
│ ~25% recur after first episode. Risk increases with │
│ each recurrence. │
│ │
│ **FIRST RECURRENCE** │
│ - **Fidaxomicin 200mg BD x 10 days** (Preferred) OR │
│ - Vancomycin tapered/Pulsed regimen: │
│ 125mg QDS x 10-14 days → 125mg BD x 7 days → │
│ 125mg OD x 7 days → 125mg Every 2-3 days x 2-8 weeks │
│ │
│ **MULTIPLE RECURRENCES (≥2)** │
│ - **Fecal Microbiota Transplantation (FMT)** │
│ - Highly effective (~90% cure) │
│ - Via colonoscopy, NG tube, Or capsules │
│ - Bezlotoxumab (Monoclonal Ab vs Toxin B) – Reduces │
│ recurrence risk (Adjunct) │
└──────────────────────────────────────────────────────────┘
7. Complications
| Complication | Notes |
|---|---|
| Recurrence | ~25% after first episode. ~40% after first recurrence. Major clinical problem. |
| Toxic Megacolon | Colonic dilatation >6cm. Ileus. Systemic toxicity. Risk of perforation. Surgical emergency. |
| Perforation | Peritonitis. High mortality. |
| Sepsis / Septic Shock | |
| Death | ~5% overall. Higher in fulminant. |
| Dehydration / AKI | From diarrhoea. |
8. Prognosis and Outcomes
| Factor | Notes |
|---|---|
| Mortality | ~5% overall. ~15-20% severe/Fulminant. |
| Recurrence | ~25% after first episode. High burden. |
| FMT Success | ~85-90% for recurrent CDI. |
9. Prevention
| Measure | Notes |
|---|---|
| Antibiotic Stewardship | Reduce unnecessary antibiotic use. Short courses. Narrow spectrum where possible. |
| Infection Control | Isolation. Soap and water hand hygiene. Personal protective equipment. Environmental cleaning (Sporicidal). |
| PPI Review | Stop if not indicated. |
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| CDI | IDSA/SHEA 2021, PHE/NICE | Vancomycin or Fidaxomicin first-line. FMT for recurrent. Infection control. Antibiotic stewardship. |
11. Patient and Layperson Explanation
What is C. diff Infection?
C. diff (Clostridioides difficile) is a germ that can cause severe diarrhoea and inflammation of the bowel. It often happens after taking antibiotics, Which can upset the normal balance of bacteria in your gut.
What are the symptoms?
- Watery diarrhoea (Often many times a day).
- Stomach cramps and pain.
- Fever.
- Nausea.
- Loss of appetite.
How is it treated?
- Stopping unnecessary antibiotics.
- Specific antibiotics: Oral Vancomycin or Fidaxomicin kill C. diff.
- Fluids: To prevent dehydration.
- For people who keep getting it back, A special treatment called Fecal Microbiota Transplant (FMT) can be very effective.
How is it spread?
C. diff spores spread through contact with contaminated surfaces or hands. In hospitals, It can spread if hand hygiene and cleaning are not thorough. Soap and water must be used – Alcohol hand gel doesn't kill the spores.
How can I prevent it?
- Only take antibiotics when truly needed.
- Good hand hygiene.
12. References
Primary Sources
- 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.
- Johnson S, et al. Clinical Practice Guideline by the IDSA and SHEA: 2021 Focused Update Guidelines on Management of CDI. Clin Infect Dis. 2021;73(5):e1029-e1044. PMID: 34164674.
- Public Health England. Updated guidance on the management and treatment of Clostridium difficile infection. 2013.
13. Examination Focus
Common Exam Questions
- First-Line Treatment: "What is the first-line antibiotic treatment for non-severe CDI?"
- Answer: Oral Vancomycin 125mg QDS for 10 days OR Fidaxomicin 200mg BD for 10 days (Fidaxomicin preferred for lower recurrence).
- Hand Hygiene: "Why is alcohol hand gel ineffective against C. diff?"
- Answer: Alcohol does NOT kill C. difficile Spores. Soap and Water must be used.
- Recurrent CDI Treatment: "What is the most effective treatment for multiple recurrent CDI?"
- Answer: Fecal Microbiota Transplantation (FMT).
- Severity Marker: "What laboratory finding indicates severe CDI?"
- Answer: WCC ≥15,000/µL OR Creatinine ≥1.5x baseline.
Viva Points
- IV Vancomycin Does NOT Treat CDI: Does not reach colon. Use Oral Vancomycin.
- Avoid Loperamide: Risk of toxic megacolon.
- Fidaxomicin = Lower Recurrence: Preferred if available.
- Fulminant = Oral + Rectal Vancomycin + IV Metronidazole + Surgical Consult.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.