What is the recommended approach if diarrhea returns after treatment for Clostridioides difficile (C. diff) infection, should I retest or retreat?

Management of Recurrent Diarrhea After C. difficile Treatment

If diarrhea returns after treatment for C. difficile infection, you should retest the patient before initiating retreatment. 1

Diagnostic Approach for Recurrent Diarrhea

When a patient experiences diarrhea after completing treatment for C. difficile infection (CDI), follow this algorithm:

1. Confirm recurrent CDI with testing:

   • Obtain stool sample for C. difficile testing
   • Testing should ideally include toxin detection, not just PCR/NAAT alone 1
   • Recurrent CDI is defined as clinically significant diarrhea (≥3 loose stools in 24 hours) with a confirmatory positive test within 8 weeks of completing antibiotics 1

2. Rule out alternative diagnoses:

   • Consider other causes of diarrhea, especially if symptoms are atypical (e.g., alternating diarrhea/constipation)
   • Be suspicious of alternative diagnoses if there was no response to initial vancomycin or fidaxomicin treatment 1

Key Considerations

• Do not treat empirically without testing: Empiric treatment without confirmatory testing is discouraged as it may be unnecessary and potentially harmful to microbiome restoration 1

• Avoid repeat testing within 7 days of the same diarrheal episode unless there are clear changes in clinical presentation 1

• Do not test for cure: There is no clinical value in repeat testing to establish cure; >60% of patients may remain C. difficile positive even after successful treatment 1

Treatment Algorithm for Confirmed Recurrent CDI

1. First recurrence:

   • Use oral vancomycin 125 mg four times daily for 10 days 1
   • Alternative: fidaxomicin 200 mg twice daily for 10 days 1

2. Second or subsequent recurrences:

   • Vancomycin 125 mg four times daily for at least 10 days 1
   • Consider vancomycin taper/pulse strategy (decreasing daily dose with 125 mg every 3 days or a dose of 125 mg every 3 days for 3 weeks) 1
   • Consider fecal microbiota-based therapies after completion of standard antibiotics 1

Important Clinical Pitfalls

• Persistent altered bowel habits: Patients can have reduced health scores for months after CDI and may experience altered bowel habits for prolonged periods 1

• False recurrence: In one study, 35% of CDI patients with recurrent diarrhea tested negative for C. difficile toxin 1

• Continued environmental shedding: Skin contamination and environmental shedding of C. difficile often persist at the time of resolution of diarrhea, and recurrent shedding is common 1-4 weeks after therapy 2

• Risk factors for true recurrence: Use of antibiotics for non-CDI indications after treatment increases risk of recurrence 2

By following this evidence-based approach, you can properly distinguish between true CDI recurrence requiring retreatment and other causes of post-treatment diarrhea, leading to better patient outcomes and reduced unnecessary antibiotic use.