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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
Key points
- C difficile causes watery diarrhea after antibiotics, hospitalization, older age, PPI exposure, or healthcare contact
- Test only symptomatic patients with unexplained new diarrhea; do not test formed stool or cure-test
- Preferred initial therapy: fidaxomicin; oral vancomycin acceptable alternative
- Fulminant CDI: hypotension, shock, ileus, or megacolon — high-dose oral/NG vancomycin plus IV metronidazole
- Recurrent CDI may require fidaxomicin, vancomycin taper, bezlotoxumab, or fecal microbiota therapy
Overview
C difficile infection occurs when antibiotic-mediated microbiome disruption allows toxigenic C difficile proliferation. Toxins A and B cause colonic inflammation, secretory diarrhea, pseudomembranes, and severe systemic illness.
Epidemiology
Risk factors include clindamycin, cephalosporins, fluoroquinolones, broad-spectrum penicillins, hospitalization, nursing facility residence, age >65, immunosuppression, IBD, PPI exposure, and prior CDI.
Clinical Features
Symptoms
Watery diarrhea, often >=3 unformed stools in 24 h
Lower abdominal cramping, fever, nausea
Recent antibiotics or hospitalization
Severe pain, ileus, abdominal distension, hypotension
Bloody diarrhea is less typical
Signs
Fever, abdominal tenderness
Dehydration and tachycardia
Marked leukocytosis
Peritonitis, shock, toxic megacolon
Investigations
First-line
Stool toxin/NAAT algorithmTest diarrheal stool only; NAAT may detect colonization
CBC, BMP, creatinineSeverity: WBC >=15,000 or creatinine rise
Medication reviewStop inciting antibiotic and unnecessary PPI if possible
Second-line
CT abdomenIf severe pain, ileus, megacolon, perforation concern
Flexible sigmoidoscopyRare; pseudomembranes if diagnosis uncertain and ileus prevents stool testing
Specialist
Surgical consultationFulminant colitis, megacolon, perforation, rising lactate, shock
Infectious diseases/GIMultiple recurrences or fecal microbiota therapy
Management
IDSA/SHEA 2021 Focused Update for CDI1
Initial non-fulminant CDI
- Stop unnecessary inciting antibiotics
- Fidaxomicin preferred when available
- Oral vancomycin acceptable alternative
2
Fulminant CDI
- High-dose oral/NG vancomycin plus IV metronidazole
- Add rectal vancomycin if ileus
- Early surgery for toxic megacolon, perforation, shock
3
Recurrence
- Fidaxomicin or vancomycin taper/pulse depending prior regimen
- Bezlotoxumab for high recurrence risk
- Fecal microbiota therapy for multiple recurrences
Complications
- Fulminant colitis: Shock, ileus, megacolon.
- Toxic megacolon: Colonic dilation with systemic toxicity.
- Perforation: Surgical emergency.
- Recurrence: Persistent spores and dysbiosis.
USMLE Step 2 CK Exam Tips
- 1Antibiotic-associated watery diarrhea + leukocytosis = C difficile
- 2Do not test formed stool; do not test for cure
- 3Fidaxomicin preferred; oral vancomycin acceptable
- 4Metronidazole alone is no longer preferred initial adult therapy
- 5Fulminant CDI needs oral/NG vancomycin plus IV metronidazole
- 6Ileus? add rectal vancomycin
- 7Pseudomembranes are classic but not required
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