Bedside Rounds

Clostridioides difficile infection: workup and management

C. difficile infection: ≥3 unformed stools in 24 hours with a positive toxin or toxin-gene test, usually after antibiotics or healthcare exposure. Test only patients with new unexplained diarrhea not on laxatives, grade the severity, and treat with fidaxomicin or oral vancomycin.

Working diagnosis Adult · US guidelines Draft · awaiting physician review
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01Orient

What's new in the evidence

  • Fidaxomicin remains preferred for initial and recurrent episodes (IDSA/SHEA 2021, ACG 2021)
  • Bezlotoxumab (Zinplava) has been discontinued in the US
  • Live biotherapeutics are FDA-approved to prevent recurrence after antibiotic treatment: fecal microbiota live-jslm (rectal) and fecal microbiota spores live-brpk (oral)

Differential diagnoses

  1. C. difficile infection
  2. Fulminant colitis or toxic megacolon (can't miss)
  3. Laxative, enteral feeds or medication-related diarrhea
  4. Other infectious diarrhea (norovirus, Salmonella, CMV in immunocompromised)
  5. Inflammatory bowel disease flare
  6. Ischemic colitis

02Assess

Risk scores and decision tools

  • Severity: WBC ≥15,000/µL or creatinine >1.5 mg/dL = severe
  • Fulminant: hypotension, shock, ileus or megacolon
  • Bristol stool chart to confirm unformed stools before testing

Key history questions

  • Number and character of stools; blood
  • Antibiotics in the last 3 months; PPI use
  • Recent hospitalization or nursing home stay
  • Laxatives or stool softeners in the past 48 hours
  • Prior C. difficile episodes and treatment
  • Abdominal pain, distension, fever

Examination findings

  • Fever, tachycardia, hypotension
  • Abdominal tenderness, distension, peritonism
  • Reduced bowel sounds or ileus (fulminant disease)

03Investigate

Initial investigations

  • Stool C. difficile test per lab algorithm (GDH/toxin EIA with NAAT, or NAAT if pre-screened)
  • CBC (WBC ≥15,000/µL means severe), creatinine (>1.5 mg/dL means severe), lactate
  • Albumin

Advanced investigations

  • CT abdomen if fulminant, distension or ileus
  • Do not repeat testing within 7 days or as a test of cure

04Treat

Immediate management

  • Contact precautions with soap-and-water hand hygiene
  • Stop unnecessary antibiotics and PPIs
  • Fulminant (hypotension, shock, ileus or megacolon): vancomycin 500 mg PO/NG four times daily plus metronidazole 500 mg IV every 8 hours; rectal vancomycin if ileus; surgical consult

First-line treatment

  • Initial episode: fidaxomicin 200 mg twice daily for 10 days (preferred)
  • Alternative: vancomycin 125 mg PO four times daily for 10 days
  • Metronidazole only if neither is available, for non-severe disease

Second-line treatment

  • First recurrence: fidaxomicin (standard or extended-pulsed), or vancomycin tapered and pulsed
  • Multiple recurrences: vancomycin taper or fidaxomicin, then a live biotherapeutic or fecal microbiota transplantation
  • Fulminant colitis not improving: early surgical consultation (subtotal colectomy or diverting loop ileostomy)

Specialist referrals

  • General surgery for fulminant colitis
  • Infectious diseases or gastroenterology for recurrent disease

05Disposition

Admission criteria

  • Severe or fulminant disease
  • Dehydration, AKI, unable to take oral medication
  • Frail or immunocompromised

Safe discharge criteria

  • Non-severe disease, tolerating oral therapy
  • Able to stay hydrated; access to medication (fidaxomicin cost checked)

Follow-up timing

  • Phone or clinic follow-up within 1 week

Patient instructions

  • Wash hands with soap and water; alcohol gel does not kill spores
  • Avoid unnecessary antibiotics in future; tell clinicians about this infection
  • Return for bloody stool, severe pain, fever or reduced urine

Monitoring

  • Stool frequency, fluid balance, WBC and creatinine

Clinical pearls and pitfalls

  • Colonization is common; testing formed stool or patients on laxatives causes overdiagnosis
  • Recurrence is common (about 20%), usually within 8 weeks
  • Diarrhea may take several days to settle on effective therapy

RefGuidelines and landmark evidence

For education only. Typical adult starting points; confirm doses against renal function, allergies, interactions and your institution's protocols. Not a substitute for clinical judgment or senior review.

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