What is the treatment approach for recurrent Clostridioides difficile (C diff) colitis?

Treatment of Recurrent Clostridioides difficile Colitis

For recurrent C. difficile infection, use oral vancomycin 125 mg four times daily for 10-14 days followed by a prolonged taper/pulse regimen for the first recurrence, and strongly consider fecal microbiota transplantation (FMT) after the second recurrence, as FMT achieves >85% cure rates compared to 40-50% with antibiotics alone. 1, 2

First Recurrence Management

Repeat the initial antibiotic therapy with either vancomycin or fidaxomicin—do not use metronidazole for any recurrence due to neurotoxicity and hepatotoxicity risks. 1, 3

• Vancomycin 125 mg orally four times daily for 10-14 days is the standard approach 1, 4
• Fidaxomicin 200 mg orally twice daily for 10 days is an alternative that reduces recurrence rates compared to vancomycin, particularly in high-risk patients (elderly, multiple comorbidities, concurrent antibiotics) 1
• Add bezlotoxumab 10 mg/kg IV as a single dose during antibiotic treatment if the patient has high recurrence risk factors (age ≥65, immunocompromised, severe CDI, hypervirulent strain, or history of prior CDI) 5, 6

Second and Subsequent Recurrences

After a second recurrence, use vancomycin with an extended taper/pulse regimen OR proceed directly to FMT. 1

Vancomycin Taper/Pulse Protocol:

• 125 mg every 6 hours × 10-14 days
• Then 125 mg every 12 hours × 7 days
• Then 125 mg every 24 hours × 7 days
• Then 125 mg every 48-72 hours × 2-8 weeks 1, 3

Fecal Microbiota Transplantation Criteria:

FMT should only be considered after recurrence following resolution of an episode treated with appropriate antimicrobials for at least 10 days—never as initial therapy. 1

• FMT is recommended after failure of at least two standard antibiotic courses 1
• For severe or complicated CDI, consider FMT only after failure of three courses of antibiotics 1
• Success rates exceed 85% for multiply recurrent CDI 2
• If first FMT fails, repeat FMT has excellent success rates—can be administered as soon as 24-72 hours after initial FMT for non-response 1

Critical Management Principles

Before considering FMT, trial extended/pulsed vancomycin AND fidaxomicin, as these medications reduce recurrence risk compared to standard dosing. 1

• Discontinue the inciting antibiotic immediately if CDI was clearly antibiotic-induced 1, 4
• If continued antibiotics are required for another infection, use agents less associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 1
• Avoid antiperistaltic agents and opiates entirely—they worsen outcomes by promoting toxin retention and increasing toxic megacolon risk 5, 4
• Consider discontinuing proton pump inhibitors if not medically necessary, as PPIs are associated with increased CDI recurrence 1

Fulminant Disease Considerations

If recurrent CDI presents as fulminant disease (hypotension, ileus, megacolon, hemodynamic instability):

• High-dose oral vancomycin 500 mg four times daily PLUS IV metronidazole 500 mg every 8 hours 5
• Add rectal vancomycin 500 mg in 100 mL normal saline every 4-12 hours if ileus is present 5
• Urgent surgical consultation for colectomy if: colonic perforation, systemic inflammation not responding to antibiotics, toxic megacolon, severe ileus, or serum lactate >5.0 mmol/L 5, 4

Common Pitfalls to Avoid

• Never use metronidazole for recurrent CDI—it is inferior to vancomycin and carries neurotoxicity/hepatotoxicity risks with repeated courses 1, 3
• Do not perform "test of cure" after CDI treatment—laboratory testing cannot distinguish colonization from infection 1
• Do not use FMT as initial therapy—it should only follow appropriate antibiotic trials 1
• Avoid fluoroquinolones for concurrent infections—they significantly increase CDI recurrence risk 7
• For FMT failure with pseudomembranous colitis, restart 5 days of vancomycin before offering another FMT 1