What are the guidelines for diagnosing and treating Clostridioides (C. diff) infection?

Diagnosis and Treatment of Clostridioides difficile Infection (CDI)

The diagnosis of C. difficile infection requires both the presence of compatible symptoms (typically diarrhea) and laboratory evidence of toxigenic C. difficile or its toxins in stool, using a recommended two-step testing protocol for optimal accuracy. 1, 2

Diagnostic Approach

When to Test

• Test only unformed stool samples from symptomatic patients (≥3 unformed stools in 24 hours) 1
• Test all patients with potential infective diarrhea after negative tests for common enteropathogens 1
• Always test patients who have been hospitalized >72 hours with diarrhea 1
• Test patients who develop diarrhea within 3 months after healthcare facility admission 1
• Do not test asymptomatic patients 1, 2
• Do not perform "test of cure" after treatment completion 2

Recommended Testing Algorithm

1. First step screening (one of the following):

   • EIA detecting glutamate dehydrogenase (GDH)
   • EIA detecting toxins A and B
   • Nucleic acid amplification test (NAAT) detecting toxin B gene (TcdB) 1

2. Second step confirmation (if first test is positive):

   • If GDH or NAAT positive: confirm with toxin detection test
   • If toxin test positive: confirm with GDH or NAAT 1

3. Interpretation:

   • Negative first test: Report as negative for CDI
   • Positive first test + positive confirmatory test: Report as positive for CDI
   • Positive first test + negative confirmatory test: Cannot differentiate between infection and colonization 1

Clinical Assessment

Symptoms and Signs

• Diarrhea (≥3 loose/unformed stools in 24 hours)
• Abdominal pain, cramping, distension
• Fever, rigors, nausea, loss of appetite, malaise in severe cases 2

Laboratory Findings

• Marked leukocytosis
• Left shift
• Elevated serum creatinine
• Elevated serum lactate
• Hypoalbuminemia 2

Risk Factors

• Recent antibiotic exposure (especially clindamycin, fluoroquinolones, cephalosporins)
• Advanced age (≥65 years)
• Healthcare facility exposure
• Serious comorbidities
• Proton pump inhibitor use 2

Treatment Recommendations

Initial Episode (Non-severe)

• First-line: Fidaxomicin 200 mg orally twice daily for 10 days 2, 3
• Alternative: Vancomycin 125 mg orally four times daily for 10 days 1, 2
• Metronidazole is no longer recommended as first-line therapy 2, 4

Severe CDI

• Vancomycin 125 mg orally four times daily for 10 days 1, 2
• Consider increasing to 500 mg four times daily for severe cases 2
• Add rectal vancomycin if ileus is present 2

Fulminant CDI

• Vancomycin 500 mg orally or via nasogastric tube four times daily
• Plus metronidazole 500 mg IV every 8 hours
• Plus vancomycin 500 mg in 100 mL normal saline as rectal instillation every 6 hours if ileus present 2

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days
• Alternative: Fidaxomicin 200 mg twice daily for 5 days, then once every other day for 20 days
• Alternative: Vancomycin in a tapered and pulsed regimen 1, 2

Multiple Recurrences

• Vancomycin tapered and pulsed regimen
• Vancomycin followed by rifaximin
• Fecal microbiota transplantation (FMT) after failure of appropriate antibiotic treatments for at least two recurrences 1, 2, 5

Adjunctive Therapy

• Bezlotoxumab 10 mg/kg IV once during standard antibiotic treatment for patients at high risk for recurrence 1, 2

Surgical Management

• Consider surgical intervention for:
  • Colonic perforation
  • Systemic inflammation with deteriorating clinical condition despite maximal therapy
  • Toxic megacolon
  • Acute abdomen
  • Severe ileus 2

Prevention and Control

• Hand hygiene with soap and water (preferred during outbreaks)
• Contact precautions for symptomatic patients
• Environmental cleaning with sporicidal agents
• Discontinue unnecessary antibiotics and proton pump inhibitors
• Implement antimicrobial stewardship programs 2

Common Pitfalls to Avoid

• Testing asymptomatic patients
• Using metronidazole as first-line therapy for severe CDI
• Failing to assess disease severity
• Treating asymptomatic carriers
• Performing "test of cure" after treatment
• Not considering risk factors for recurrence 2

Remember that diagnosis requires both symptoms and laboratory confirmation, and treatment should be tailored based on severity, episode number, and risk factors for recurrence.