Treatment for C. difficile Colitis After Vancomycin Failure
For patients who have failed oral vancomycin, fidaxomicin 200 mg twice daily for 10 days is the preferred treatment for first recurrence, while fecal microbiota transplantation (FMT) should be pursued after multiple recurrences. 1
First Recurrence After Vancomycin Failure
Fidaxomicin 200 mg orally twice daily for 10 days is the recommended first-line treatment when vancomycin was used for the initial episode, as it demonstrates lower recurrence rates compared to repeating vancomycin 1, 2
Vancomycin tapered and pulsed regimen is an effective alternative, consisting of 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks 1, 2
Avoid metronidazole for recurrent CDI due to lower sustained response rates and risk of cumulative neurotoxicity with repeated or prolonged courses 1, 2
Multiple Recurrences (Second or Subsequent)
Fecal microbiota transplantation (FMT) is highly effective and recommended after at least 2 recurrences when patients have failed appropriate antibiotic treatments 1, 2
Vancomycin extended pulsed regimen remains an option for patients who cannot access FMT or prefer antibiotic therapy 1, 2
Adjunctive Therapy to Prevent Further Recurrence
- Bezlotoxumab (human monoclonal antibody against C. difficile toxin B) reduces recurrent CDI and is particularly beneficial for high-risk patients including those with the 027 epidemic strain, immunocompromised status, or severe CDI presentation 1
Special Situations: Severe or Fulminant Disease
If the patient has severe disease manifestations (hypotension, shock, ileus, toxic megacolon) despite vancomycin failure:
Increase vancomycin dose to 500 mg orally four times daily plus add intravenous metronidazole 500 mg three times daily 3, 2, 4
Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema if ileus is present or oral medication cannot reach the colon 3, 4
Consider intracolonic vancomycin via nasogastric tube or trans-stoma administration in patients with ileostomy, colostomy, or Hartmann resection 3, 5, 6
Early surgical consultation is essential for patients with systemic toxicity, rising lactate, progressive organ failure, or worsening abdominal distension 4
Alternative Salvage Therapies
For patients not responding to standard approaches:
Intravenous tigecycline may be considered as salvage therapy in refractory cases 1, 4
Intravenous immunoglobulins (passive immunotherapy) can be considered for patients failing standard treatments 1, 4
Critical Supportive Measures
Discontinue the inciting antibiotic immediately if still being administered, as failure to stop offending antibiotics is associated with CDI recurrence 3, 2
Provide aggressive supportive care including intravenous fluid resuscitation, electrolyte replacement, and albumin supplementation in patients with severe hypoalbuminemia 1, 4
Common Pitfalls to Avoid
Do not repeat standard-dose vancomycin at the same regimen that already failed—either escalate to fidaxomicin, use tapered/pulsed vancomycin, or pursue FMT 1, 2
Do not use metronidazole for recurrent disease, as it has inferior efficacy and cumulative neurotoxicity risk 1, 2
Do not delay surgical consultation in fulminant cases, as early surgery improves outcomes when medical therapy fails 3, 4
Recognize that intravenous vancomycin has no effect on CDI since it is not excreted into the colon—only enteral or intracolonic routes are effective 3