How soon after starting oral vancomycin for a positive Clostridiium difficile (C. difficile) stool test can a stool test be repeated if diarrhea is still present?

Do Not Repeat C. difficile Testing Within 7 Days After Starting Vancomycin

Do not perform repeat C. difficile testing within 7 days during the same episode of diarrhea, even if symptoms persist after starting oral vancomycin treatment. 1

Rationale for Not Repeating Testing

• Repeat testing within 7 days of a negative result during the same diarrheal episode has very low diagnostic yield (approximately 2%) and is not recommended 1
• Testing within 7 days after starting treatment is not useful as >60% of patients may remain C. difficile positive even after successful treatment 1
• The proportion of subjects transitioning from negative to positive C. difficile results within a 7-day window is only 3% (95% CI, 0.023 to 0.038) 1
• The Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) strongly recommend against repeat testing within 7 days during the same episode of diarrhea 1

Clinical Approach to Persistent Diarrhea After Starting Vancomycin

Assessment of Treatment Response

• Most patients (87%) show a decrease in temperature, abdominal pain, and diarrhea within 48 hours of starting vancomycin therapy 2
• Diarrhea typically ceases completely within 2-7 days in most patients receiving oral vancomycin 2, 3
• Persistence of symptoms beyond this timeframe should prompt consideration of alternative diagnoses rather than repeat C. difficile testing 1

Alternative Explanations for Persistent Diarrhea

• Consider other causes of diarrhea, particularly if symptoms are atypical (e.g., diarrhea alternating with constipation) 1
• Evaluate for possible cytomegalovirus colitis, which can complicate C. difficile infection 4
• Post-infectious irritable bowel syndrome can occur following C. difficile infection 1
• Inflammatory bowel disease flare may coexist with or mimic persistent C. difficile infection 1

When to Consider Repeat Testing

• Repeat testing should only be considered after at least 7 days if there is a clear change in the clinical presentation or strong clinical suspicion 1, 5
• For recurrence of symptoms following successful treatment and diarrhea cessation (typically defined as recurrence within 8 weeks of completing antibiotics), repeat testing is appropriate 1
• Testing for recurrent CDI should ideally include toxin detection, as persistence of toxigenic C. difficile can occur commonly after infection 1

Treatment Considerations for Persistent Symptoms

• If diarrhea persists despite appropriate vancomycin therapy, consider:
  • Increasing the vancomycin dose (250 mg or 500 mg four times daily), which leads to consistently higher fecal levels (>2000 mg/L) 6
  • Evaluating for complications such as severe or fulminant C. difficile infection that may require additional interventions 1
  • Assessing for vancomycin-resistant organisms that may be contributing to treatment failure 4

Common Pitfalls to Avoid

• Empiric treatment without confirmatory testing of suspected recurrence is discouraged 1
• Avoid "test of cure" as >60% of patients may remain C. difficile positive even after successful treatment 1, 7
• Do not test asymptomatic patients, even with a history of C. difficile 5
• Be aware that patients with increased stool frequency may have lower fecal vancomycin levels, but these are still orders of magnitude higher than the MIC90 of vancomycin against C. difficile 6

Remember that clinical improvement, rather than microbiological clearance, is the goal of therapy for C. difficile infection. Persistent positive tests do not necessarily indicate treatment failure if symptoms are resolving.