What is the recommended workup and treatment for a patient with suspected Clostridioides difficile (C diff) infection?

Workup and Treatment for Clostridioides difficile Infection

For patients with suspected C. difficile infection (CDI), diagnostic testing should be performed only in symptomatic patients with unexplained diarrhea (≥3 unformed stools in 24 hours), and treatment should be based on disease severity, with oral vancomycin or fidaxomicin as first-line therapy for initial episodes. 1

Diagnostic Approach

When to Test

• Test only symptomatic patients with:
  • ≥3 unformed stools in 24 hours 1
  • Not taking laxatives 2
  • Risk factors: recent antibiotic exposure, healthcare facility exposure, age >65, immunocompromising conditions 1, 3

Testing Strategy

1. Preferred testing approach: Multistep algorithm using:

   • Glutamate dehydrogenase (GDH) antigen AND toxin A/B enzyme immunoassay (EIA) 1
   • If discordant results (GDH+/toxin-), perform nucleic acid amplification test (NAAT) 4

2. Alternative approach: Single-step NAAT (PCR) on liquid stool 1

3. Special populations:

   • Children <12 months: Testing not recommended (high asymptomatic carriage) 1
   • Children 1-2 years: Test only after excluding other causes 1
   • Children ≥2 years: Test if prolonged/worsening diarrhea AND risk factors present 1

Additional Diagnostic Considerations

• "Test of cure" is NOT recommended after treatment 1
• Consider colonoscopy only when:
  • High clinical suspicion with negative stool tests
  • Need for immediate diagnosis
  • Concern for other conditions (e.g., IBD) 4, 5

Treatment Algorithm

Initial Episode

1. Non-severe CDI:

   • First-line: Oral vancomycin 125 mg QID for 10 days OR fidaxomicin 200 mg BID for 10 days 1
   • If limited access to vancomycin/fidaxomicin: Oral metronidazole 500 mg TID for 10 days (avoid prolonged/repeated courses due to neurotoxicity risk) 1
   • Stop inciting antibiotics if possible 1

2. Severe CDI (WBC ≥15,000 cells/mm³ OR serum creatinine ≥1.5 mg/dL):

   • Oral vancomycin 125 mg QID for 10 days 1

3. Fulminant CDI (hypotension, shock, ileus, megacolon):

   • Oral vancomycin 500 mg QID 1
   • PLUS intravenous metronidazole 500 mg every 8 hours 1
   • If ileus present: Add vancomycin 500 mg in 100 mL normal saline by retention enema Q6H 1
   • Consider surgical consultation for possible colectomy if:
     • Perforation
     • Systemic inflammation not responding to antibiotics
     • Serum lactate >5.0 mmol/L 1

Recurrent CDI

1. First recurrence:

   • If initial treatment was metronidazole: Vancomycin 125 mg QID for 10 days 1
   • If initial treatment was vancomycin: Vancomycin taper or fidaxomicin 200 mg BID for 10 days 1

2. Second or subsequent recurrence:

   • Vancomycin taper/pulse regimen:
     • 125 mg QID for 10-14 days, then
     • 125 mg BID for 7 days, then
     • 125 mg daily for 7 days, then
     • 125 mg every 2-3 days for 2-8 weeks 1
   • OR fidaxomicin 200 mg BID for 10 days 1
   • OR consider fecal microbiota transplantation (FMT) after appropriate antibiotic therapy for at least three recurrent episodes 1, 2

Infection Control Measures

1. Contact Precautions:

   • Implement for all suspected/confirmed CDI patients 1
   • Use gloves and gowns when entering patient rooms 1
   • Continue for at least 48 hours after diarrhea resolves 1
   • Private room with dedicated toilet when possible 1

2. Hand Hygiene:

   • In routine settings: Soap and water OR alcohol-based hand sanitizer 1
   • During outbreaks: Preferentially use soap and water (better spore removal) 1

3. Environmental Cleaning:

   • Use sporicidal disinfectants for daily cleaning 1
   • Terminal room cleaning with sporicidal agents 1
   • Use disposable equipment when possible 1

Prevention Strategies

1. Antibiotic Stewardship:

   • Minimize frequency and duration of high-risk antibiotics 1
   • Target restriction of fluoroquinolones, clindamycin, and cephalosporins 1

2. Other Considerations:

   • Discontinue unnecessary proton pump inhibitors (PPI) 1
   • Probiotics are not recommended for prevention of CDI 2

Common Pitfalls to Avoid

1. Diagnostic pitfalls:

   • Testing formed stool (high false-positive rate)
   • Testing asymptomatic patients
   • Testing children <12 months (high colonization rate)
   • Performing "test of cure"

2. Treatment pitfalls:

   • Using metronidazole for severe or recurrent CDI
   • Continuing inciting antibiotics when unnecessary
   • Failing to assess severity to guide therapy
   • Using antiperistaltic agents (should be avoided) 1

3. Infection control pitfalls:

   • Premature discontinuation of contact precautions
   • Relying solely on alcohol-based hand sanitizers during outbreaks
   • Inadequate environmental cleaning

By following this evidence-based approach to diagnosis and treatment of CDI, clinicians can optimize patient outcomes while minimizing the risk of recurrence and transmission.