What is the best treatment for chronic diarrhea with elevated calprotectin and prior C-diff infection?

Management of Chronic Diarrhea with Elevated Calprotectin and Prior C. difficile Infection

For a patient with chronic diarrhea, elevated calprotectin (431), and prior C. difficile infection but currently negative C. difficile testing, oral vancomycin using a tapered and pulsed regimen is the recommended treatment approach. 1

Assessment of Current Condition

The clinical presentation suggests two potential overlapping conditions:

1. Possible recurrent C. difficile infection (RCDI)

   • Prior positive C. difficile history
   • Current negative C. difficile test (may be false negative)
   • Chronic diarrhea

2. Possible inflammatory bowel disease (IBD)

   • Significantly elevated fecal calprotectin (431)
   • Chronic diarrhea

Diagnostic Interpretation

The elevated calprotectin level (431) strongly suggests active intestinal inflammation. According to AGA guidelines, a fecal calprotectin >150 mg/g indicates active inflammation and warrants treatment adjustment 1. The negative C. difficile test does not completely rule out recurrent infection, as symptoms may persist despite negative testing, especially in patients with prior C. difficile infection.

Treatment Algorithm

Step 1: Treat for Recurrent C. difficile Infection

• First-line treatment: Oral vancomycin 125 mg four times daily for 14 days followed by a tapered and pulsed regimen 1

  • Tapered regimen example:
    • 125 mg twice daily for 7 days
    • 125 mg once daily for 7 days
    • 125 mg every other day for 7 days
    • 125 mg every 3 days for 14 days

• Alternative treatment: Fidaxomicin 200 mg twice daily for 10 days 1, 2

  • Consider this option particularly for patients at high risk for recurrence

Step 2: If No Improvement After 3-5 Days

• Consider endoscopic evaluation to assess for:
  • Pseudomembranous colitis
  • Inflammatory bowel disease
  • Other causes of chronic diarrhea 1

Step 3: Supportive Measures

• Fluid and electrolyte replacement
• Albumin supplementation if hypoalbuminemia is present (<2 g/dL) 1
• Consider probiotics as adjunctive therapy (limited evidence) 1

Rationale for Treatment Selection

1. Why vancomycin over metronidazole:

   • Metronidazole is no longer recommended as initial treatment for recurrent CDI due to lower sustained response rates 1
   • Metronidazole should not be used for long-term therapy due to potential cumulative neurotoxicity 1
   • Vancomycin has shown superior efficacy in treating C. difficile infections 1

2. Why tapered/pulsed regimen:

   • Tapered and pulsed vancomycin regimens are more effective than standard courses for recurrent C. difficile 1
   • This approach helps eliminate persistent spores that may cause recurrence 3

3. Why consider fidaxomicin:

   • Fidaxomicin has been shown to be associated with a lower likelihood of CDI recurrence after a first recurrence 1
   • It's particularly useful for patients at high risk for recurrence 1, 3

Important Considerations

• Monitor for complications: Watch for signs of severe disease including leukocytosis >15,000, decreased albumin, or rising creatinine 1

• Avoid unnecessary antibiotics: Discontinue any non-essential antibiotics as continued use is associated with increased risk of CDI recurrence 1

• Endoscopic evaluation timing: If symptoms persist despite appropriate therapy, endoscopic evaluation should be performed to rule out other causes of diarrhea or confirm the diagnosis 1

• Differential diagnosis: The elevated calprotectin may indicate inflammatory bowel disease coexisting with or mimicking C. difficile infection, which would require different management 1

Follow-up Recommendations

• Reassess symptoms after 3-5 days of treatment
• Monitor calprotectin levels to assess response to therapy
• If symptoms persist or worsen, consider:
  • Alternative antibiotic regimens
  • Fecal microbiota transplantation for multiple recurrences 1
  • Bezlotoxumab (monoclonal antibody against C. difficile toxin B) to prevent recurrence 1

The combination of chronic diarrhea, elevated calprotectin, and prior C. difficile infection requires aggressive management to prevent complications and improve quality of life. The tapered vancomycin approach offers the best chance for resolution while minimizing the risk of recurrence.