Suspected C. difficile Infection
≥3 unformed stools in 24h + recent antibiotic exposure or healthcare contact
All Pathways
Infectious DiseaseManagement
Clostridioides difficile Infection Management (IDSA/SHEA 2021)
Clostridioides difficile Infection Management (IDSA/SHEA 2021): Suspected C. difficile Infection → Diagnostic Testing → Stop Inciting Antibiotics → Asse...
Pathway Overview
15 steps
Algorithm Steps
15 total
01Start 02Action Diagnostic Testing
Stool testing strategy
- NAAT (PCR) alone: Highly sensitive, may detect colonization
- Two-step algorithm (GDH/toxin then NAAT): Preferred by many
- Only test unformed stool (Bristol 5-7)
- Do NOT test for cure - avoid repeat testing <7 days
03Action Stop Inciting Antibiotics
If clinically feasible
- Discontinue unnecessary antibiotics ASAP
- Avoid antiperistaltic agents
- Contact precautions + hand hygiene with soap/water
- Identify and isolate
04Decision Assess Severity
Non-severe vs Severe vs Fulminant
- Non-severe: WBC ≤15,000, Cr <1.5
- Severe: WBC >15,000 OR Cr >1.5 (≥1.5× baseline)
- Fulminant: Hypotension, shock, ileus, megacolon
05Decision Initial or Recurrent Episode?
Recurrence = symptom return within 8 weeks of prior episode
06Action Initial Non-Severe CDI
First episode, mild-moderate
- PREFERRED: Fidaxomicin 200mg PO BID x10 days
- Alternative: Vancomycin 125mg PO QID x10 days
- Metronidazole 500mg PO TID x10-14 days (if above unavailable)
- Fidaxomicin associated with lower recurrence rates
07Decision Clinical Response
Assess by day 3-5
- Expect diarrhea improvement within 3-5 days
- Do NOT repeat stool testing to confirm cure
- Monitor for recurrence after treatment completion
08Outcome CDI Resolved
Symptom resolution
- Return to normal bowel function
- Monitor for recurrence (occurs in ~20-30%)
- Probiotics: Limited evidence for prevention
- Antibiotic stewardship to prevent future CDI
09Warning Recurrence / Non-Response
Symptoms persist or return
- Confirm with repeat testing (>7 days from last test)
- Escalate therapy per recurrence pathway
- Consider FMT/microbiome restoration
- Rule out other causes of diarrhea
10Action Initial Severe CDI
WBC >15K or Cr >1.5
- PREFERRED: Fidaxomicin 200mg PO BID x10 days
- Alternative: Vancomycin 125mg PO QID x10 days
- Avoid metronidazole for severe disease
- Close monitoring for progression to fulminant
- Path rejoins step 07Shared downstream outcome
11Action First Recurrence
Recurrence within 8 weeks
- If vancomycin used initially: Fidaxomicin 200mg BID x10 days (preferred)
- OR Extended vancomycin taper:
- 125mg QID x10-14d, then BID x7d, then daily x7d, then q2-3d x2-8wks
- OR Vancomycin 125mg QID x10d followed by rifaximin 400mg TID x20d
- Path rejoins step 07Shared downstream outcome
12Action Second or Subsequent Recurrence
Multiple recurrences
- Fidaxomicin 200mg BID x10 days, OR
- Vancomycin taper as above, OR
- FMT (Fecal Microbiota Transplant) recommended after ≥2 recurrences
- FDA-approved microbiome therapies: Vowst (SER-109), Rebyota (fecal microbiota, live-jslm)
13Action Fecal Microbiota Transplant/Restoration
For recurrent CDI
- Perform FMT after completion of vancomycin/fidaxomicin course
- Routes: Colonoscopy (preferred), enema, upper GI
- FDA-approved alternatives: Vowst (oral capsules), Rebyota (rectal)
- Success rate: ~80-90% for recurrent CDI
- Screen donors for pathogens
- Path rejoins step 07Shared downstream outcome
14Action Fulminant CDI
Hypotension, shock, ileus, megacolon
- Vancomycin 500mg PO/NG QID
- PLUS Metronidazole 500mg IV q8h
- If ileus: ADD Vancomycin 500mg in 100mL NS per rectum q6h
- Surgical consultation IMMEDIATELY
- Consider subtotal colectomy if refractory
15Warning Surgical Indications
When to consider colectomy
- Fulminant CDI not responding to medical therapy
- Toxic megacolon (colon >6cm)
- Colonic perforation
- Peritonitis, septic shock despite treatment
- Subtotal colectomy with end ileostomy preferred
- Path rejoins step 07Shared downstream outcome
Guideline Source
IDSA/SHEA 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- Testing strategy (NAAT vs toxin EIA) varies by institution
- Fidaxomicin preferred but cost may limit availability
- FMT access varies by region and institution
- Definition of severe/fulminant CDI may vary
- Bezlotoxumab discontinued as of January 2025
Applicable Regions
USEU
Version 1Next review: 2027-01-11
Next steps
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Related Resources
Frequently Asked Questions
What is the Clostridioides difficile Infection Management (IDSA/SHEA 2021)?
The Clostridioides difficile Infection Management (IDSA/SHEA 2021) is a management clinical algorithm for Infectious Disease. It provides a structured decision tree to guide clinical decision-making, based on IDSA/SHEA 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults.
What guideline is the Clostridioides difficile Infection Management (IDSA/SHEA 2021) based on?
This algorithm is based on IDSA/SHEA 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults (DOI: 10.1093/cid/ciab549).
What are the limitations of the Clostridioides difficile Infection Management (IDSA/SHEA 2021)?
Known limitations include: Testing strategy (NAAT vs toxin EIA) varies by institution; Fidaxomicin preferred but cost may limit availability; FMT access varies by region and institution; Definition of severe/fulminant CDI may vary; Bezlotoxumab discontinued as of January 2025. Individual patient factors may require deviation from these recommendations.
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