What to do if a patient with Clostridioides difficile infection (CDI) still has diarrhea after being treated with vancomycin?

Management of Persistent Diarrhea After Vancomycin Treatment for Clostridioides difficile Infection

For patients with persistent diarrhea after vancomycin treatment for Clostridioides difficile infection (CDI), switch to fidaxomicin 200 mg twice daily for 10 days or consider fecal microbiota-based therapy after completing a course of standard antibiotics. 1

Assessment of Persistent Diarrhea

Before changing therapy, it's crucial to determine whether the persistent diarrhea represents:

• True treatment failure: No improvement in diarrheal symptoms after 3-5 days of appropriate therapy 1
• Recurrent CDI: Return of symptoms with positive C. difficile toxin test within 8 weeks of completing treatment 1
• Alternative diagnosis: Consider other causes if symptoms are atypical (e.g., diarrhea alternating with constipation) or if there's no response to vancomycin 1

Treatment Algorithm for Persistent Diarrhea After Vancomycin

Step 1: Confirm CDI Diagnosis

• Ensure diagnosis was made with appropriate testing (nucleic acid amplification or glutamate dehydrogenase plus toxin enzyme immunoassay) 1
• Verify clinically significant diarrhea (≥3 unformed stools in 24 hours) 1

Step 2: First-Line Management Options

1. Switch to fidaxomicin: 200 mg twice daily for 10 days 1

   • More effective than vancomycin in patients receiving concomitant antibiotics (90.0% vs 79.4% cure rate) 2
   • Associated with lower recurrence rates compared to vancomycin 3

2. Consider vancomycin taper/pulse regimen: 1

   • 125 mg four times daily for 10-14 days, then
   • 125 mg twice daily for 7 days, then
   • 125 mg once daily for 7 days, then
   • 125 mg every 2-3 days for 2-8 weeks

Step 3: For Multiple Recurrences or Treatment Failures

1. Fecal microbiota-based therapies: Strongly recommended for patients with multiple recurrences who have failed appropriate antibiotic treatments 1

   • Options include conventional fecal microbiota transplant (FMT), fecal microbiota live-jslm, or fecal microbiota spores live-brpk 1
   • Should be given after completion of standard antibiotics (not during active treatment) 1
   • Suppressive anti-CDI antibiotics (e.g., vancomycin) should bridge until FMT is given 1

2. Extended-pulsed fidaxomicin regimen: 4

   • 200 mg twice daily for 5 days, then
   • 200 mg every other day for 20 days
   • Particularly effective for patients with multiple recurrences 4

Special Considerations

• Concomitant antibiotics: If the patient is receiving antibiotics for other infections, fidaxomicin is preferred over vancomycin (90.0% vs 79.4% cure rate) 2

• Severe CDI: Both oral vancomycin and fidaxomicin are recommended for severe CDI 1

• Immunocompromised patients: Conventional FMT is suggested for mildly to moderately immunocompromised adults with recurrent CDI 1

• Monitoring: For patients receiving oral vancomycin, be aware that clinically significant serum concentrations can occur with multiple doses, particularly in those with inflammatory bowel disorders 5

Common Pitfalls to Avoid

• Failure to discontinue inciting antibiotics: Always attempt to stop the antibiotics that may have triggered CDI, as continued use decreases clinical response and increases recurrence rates 1

• Inadequate vancomycin dosing: Ensure adequate dosing of vancomycin (125 mg four times daily); lower faecal vancomycin levels may occur during the first day of treatment, especially in patients with frequent stools 6

• Missing alternative diagnoses: Consider other causes of diarrhea if symptoms are atypical or not responding to appropriate CDI therapy 1

• Using antimotility agents: Avoid antiperistaltic agents and opiates in active CDI 1

• Delayed consideration of FMT: Don't delay consideration of fecal microbiota-based therapies for patients with multiple recurrences 1