Treatment of Persistent C. difficile Infection
For persistent or recurrent C. difficile infection, oral vancomycin using a tapered and pulsed regimen is the preferred treatment, with fidaxomicin as an alternative, and fecal microbiota transplantation reserved for multiple recurrences that have failed antibiotic therapy. 1
Defining Persistent/Recurrent CDI
Recurrent CDI occurs when stool frequency increases for two consecutive days with looser stools or new signs of severe colitis develop, with microbiological evidence of toxin-producing C. difficile after an initial treatment response. 1 Approximately 25% of patients treated for CDI will experience at least one additional episode. 1
Treatment Algorithm by Recurrence Number
First Recurrence
Treat based on disease severity with one of three options: 1
- Oral vancomycin 125 mg four times daily for 10 days using a tapered and pulsed regimen (preferred over standard 10-day course) 1, 2
- Fidaxomicin 200 mg twice daily for 10 days (preferred over standard vancomycin course due to lower recurrence rates of 15.4% vs 25.3%) 1
- Oral vancomycin 125 mg four times daily for 10 days if metronidazole was used for the primary episode (avoid repeating metronidazole due to neurotoxicity risk with repeated courses) 1, 3
The evidence strongly favors vancomycin or fidaxomicin over metronidazole for recurrent disease. 1, 3
Second and Subsequent Recurrences
For multiple recurrences, escalate therapy using these approaches: 1
- Vancomycin 125 mg four times daily orally for at least 10 days followed by a taper/pulse strategy 1, 2
- Vancomycin standard course followed by rifaximin 1
- Fidaxomicin 200 mg twice daily for 10 days 1, 4
While randomized trials for tapered/pulsed vancomycin are lacking, case series show recurrence rates of 31% with tapering and 14.3% with pulsed courses compared to 44.8% overall. 1
Fecal Microbiota Transplantation
For patients with multiple recurrences who have failed appropriate antibiotic treatments, fecal microbiota transplantation is strongly recommended. 1
- Clinical resolution occurs in 87-94% of patients after one or two FMT treatments 1
- A randomized trial showed 94% symptom resolution with vancomycin for 5 days followed by FMT versus 31% with vancomycin alone for 14 days 1
- Pre-screened frozen fecal capsules from unrelated donors achieve 90% response rates 1
Adjunctive Therapies
Bezlotoxumab
Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) for patients with high risk factors for recurrence: 1, 5
- Reduces recurrent infection rates from 26-28% to 16-17% when combined with standard antibiotic therapy 1
- Greatest benefit in patients with ≥3 risk factors: age ≥65 years, history of CDI, compromised immunity, severe CDI, or ribotype 027/078/244 1
Critical Supportive Measures
Always discontinue the inciting antibiotic as soon as possible to reduce recurrence risk. 1, 3, 5 If continued antibiotic therapy is required, select agents less associated with CDI. 2
Avoid antimotility agents (loperamide) and opiates as they may worsen outcomes and mask symptoms. 1, 3, 5
Common Pitfalls to Avoid
- Do not use metronidazole for recurrent CDI due to increasing treatment failures and cumulative neurotoxicity risk with repeated courses 3
- Do not delay FMT in patients with multiple recurrences—it has strong evidence and should not be considered a last resort 1
- Do not use probiotics as primary therapy—evidence is insufficient, though they are generally well-tolerated 1
- Monitor for surgical indications including rising WBC count (≥25,000), rising lactate (≥5 mmol/L), perforation, toxic megacolon, or severe ileus not responding to medical therapy 1
Special Considerations for Severe Recurrent Disease
If recurrent CDI presents as fulminant disease (hypotension, shock, ileus, megacolon): 2