What is the recommended management for a patient with a suspected or confirmed Clostridioides difficile (C.diff) infection, considering their medical history and potential for recurrence or severe infection?

Management of Clostridioides difficile Infection

For initial mild-to-moderate CDI, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the preferred first-line treatments, with metronidazole reserved only for situations where neither agent is available. 1

Initial Episode Management

Severity Assessment

Determine disease severity using these criteria 1:

• Severe CDI: WBC ≥15,000 cells/μL OR serum creatinine ≥1.5 mg/dL (or ≥1.5 times baseline) 1
• Fulminant CDI: Hypotension/shock, ileus, megacolon, or organ dysfunction 1
• Additional severity markers: Temperature >38.5°C, albumin <2.5 g/dL 1

Antibiotic Selection by Severity

Mild-to-Moderate CDI:

• First-line: Oral vancomycin 125 mg four times daily for 10 days 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days (preferred for high-risk recurrence patients: elderly with multiple comorbidities requiring concomitant antibiotics) 1, 2
• Only if vancomycin and fidaxomicin unavailable: Metronidazole 500 mg three times daily for 10 days 1

Severe CDI:

• Preferred: Oral vancomycin 125 mg four times daily for 10 days 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1
• Avoid metronidazole due to inferior outcomes in severe disease 1

Fulminant CDI:

• Oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours 1
• If ileus present: Consider vancomycin 500 mg per rectum every 6 hours via rectal catheter in addition to IV metronidazole 1
• Surgical consultation immediately for patients with perforation, toxic megacolon, lactate >5.0 mmol/L, or clinical deterioration despite maximal therapy 1

Critical Supportive Measures

Discontinue Inciting Factors

• Stop causative antibiotics immediately if clinically feasible—continued antibiotic use significantly increases recurrence risk 1
• If antibiotics must continue, switch to lower-risk agents: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 1
• Discontinue proton pump inhibitors unless absolutely required 1
• Never use antimotility agents (loperamide, opiates)—they can precipitate toxic megacolon 3

Infection Control

• Isolate patient in private room with contact precautions until diarrhea resolves (passage of formed stool for ≥48 hours) 1
• Hand hygiene with soap and water—alcohol-based sanitizers do not kill C. difficile spores 1
• Environmental cleaning with sporicidal agents 1

Recurrent CDI Management

First Recurrence

• Preferred: Fidaxomicin 200 mg twice daily for 10 days (superior to vancomycin for preventing subsequent recurrence: 19.7% vs 35.5%) 3, 2
• Alternative: Vancomycin 125 mg four times daily for 10 days 3

Multiple Recurrences (≥2 episodes)

Treatment hierarchy:

1. Fecal microbiota transplantation (FMT) after completion of standard antibiotic course—achieves 87-92% clinical resolution vs 40-50% with antibiotics alone 1, 4, 3

   • Offer FMT after at least 2 recurrences or earlier in high-risk patients 1, 3
   • Administer upon completion of 10-day antibiotic course 4, 3
   • Can use colonoscopy, nasojejunal tube, or FDA-approved oral formulations 3

2. Vancomycin tapered-and-pulsed regimen if FMT unavailable 4, 3:

   • 125 mg every 6 hours × 10-14 days
   • Then 125 mg every 12 hours × 7 days
   • Then 125 mg every 24 hours × 7 days
   • Then 125 mg every 48-72 hours × 2-8 weeks

3. Fidaxomicin extended-pulsed regimen: 200 mg twice daily with extended dosing 3

4. Vancomycin standard course followed by rifaximin 400 mg three times daily × 20 days 3

Adjunctive Therapy for High-Risk Recurrence

Bezlotoxumab 10 mg/kg IV as single infusion during or shortly after antibiotic completion for patients with 4, 3:

• History of CDI in past 6 months
• Age ≥65 years
• Immunocompromised state
• Severe CDI presentation

Diagnostic Considerations

When to Test

• Only test symptomatic patients with ≥3 unformed stools in 24 hours 1, 3
• Do not test for cure—PCR can remain positive for weeks despite clinical resolution 3

Empirical Therapy

• Avoid empirical therapy unless strong suspicion for severe CDI while awaiting test results 1
• If empirical treatment initiated, discontinue if testing negative 1

Diagnostic Pitfalls

• 25% of patients referred for FMT with presumed recurrent CDI have alternative diagnoses (IBS, IBD) 1
• Consider alternative diagnoses if symptoms atypical or unresponsive to vancomycin/fidaxomicin 3

Special Populations

Pediatric Patients (≥6 months)

• Weight ≥12.5 kg able to swallow tablets: Fidaxomicin 200 mg tablet twice daily × 10 days 2
• Weight-based oral suspension dosing 2:
  • 4 to <7 kg: 80 mg (2 mL) twice daily
  • 7 to <9 kg: 120 mg (3 mL) twice daily
  • 9 to <12.5 kg: 160 mg (4 mL) twice daily
  • ≥12.5 kg: 200 mg (5 mL) twice daily

Immunocompromised Patients

• FMT appears safe for mildly-to-moderately immunocompromised patients 3
• Avoid FMT in severely immunocompromised (active cytotoxic therapy, recent stem cell transplant) 3

Common Pitfalls to Avoid

1. Do not use IV vancomycin for CDI—it is not excreted into colon and has no efficacy 5
2. Avoid repeated metronidazole courses—risk of cumulative, potentially irreversible neurotoxicity 1
3. Do not delay FMT in multiply recurrent CDI—earlier intervention improves outcomes 1, 4
4. Avoid colonoscopy in fulminant colitis—increased perforation risk 1
5. Recognize Red Man Syndrome is not true vancomycin allergy—for oral vancomycin intolerance, use fidaxomicin 5