Treatment of Recurrent C. difficile Infection
For recurrent C. difficile infection, use oral vancomycin 125 mg four times daily for 10-14 days followed by a tapered and pulsed regimen for the first recurrence, and strongly consider fidaxomicin or fecal microbiota transplantation for second and subsequent recurrences. 1
First Recurrence Treatment Strategy
Treat the first recurrence with oral vancomycin using a tapered and pulsed regimen, particularly if metronidazole was used for the initial episode 1. The specific regimen is:
- Vancomycin 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 1
This approach keeps C. difficile vegetative forms suppressed while allowing restoration of normal gut microbiota 1.
Fidaxomicin 200 mg twice daily for 10 days is an excellent alternative for first recurrence, as it reduces subsequent recurrence rates compared to standard vancomycin (19.7% vs 35.5%, p=0.045) 1, 2. However, its efficacy may be lower in patients with ≥2 prior recurrences 1.
Critical Pitfall to Avoid
Do not use metronidazole for recurrent CDI 1. Initial and sustained response rates are lower than vancomycin, and metronidazole carries risk of cumulative neurotoxicity with prolonged use 1, 2.
Second and Subsequent Recurrences
For second or subsequent recurrences, the treatment hierarchy is:
Fecal microbiota transplantation (FMT) is the most effective option with strong recommendation and moderate quality evidence 1. FMT should be offered after at least 2 recurrences in patients who have failed appropriate antibiotic treatments 1, 2.
Vancomycin tapered and pulsed regimen (as described above) remains an option 1, 2.
Fidaxomicin 200 mg twice daily for 10 days can be considered, though data for multiply recurrent CDI are limited 1, 2.
Vancomycin followed by rifaximin (400 mg three times daily for 20 days after completing vancomycin) showed reduced recurrence in a small trial (15% vs 31%, p=0.11) 1.
Adjunctive Therapy: Bezlotoxumab
Consider adding bezlotoxumab (monoclonal antibody against C. difficile toxin B) to standard antibiotic therapy for patients at high risk of recurrence 2, 3, 4. This is particularly beneficial for:
- Patients ≥65 years of age
- Immunocompromised patients
- Those with severe CDI presentation
- Infection with epidemic strain 027 2, 3
Bezlotoxumab reduces recurrence rates by approximately 10-15% when added to standard antibacterial therapy 3.
Important Clinical Considerations
Discontinue inciting antibiotics whenever possible, as continued antibiotic use is associated with treatment failure and increased recurrence risk 1, 5.
Avoid proton pump inhibitors if possible, as continued PPI use increases recurrence risk 1.
Do not use antimotility agents (loperamide, opiates) as they can worsen outcomes 5.
Risk factors that predict recurrence include:
- Age ≥65 years
- Continued antibiotic use during or after CDI treatment
- Immunocompromised state
- Severe initial disease
- Defective humoral immune response to C. difficile toxins 1
When Oral Therapy is Impossible
For patients unable to take oral medications with recurrent CDI:
- Intravenous metronidazole 500 mg every 8 hours PLUS
- Vancomycin 500 mg via nasogastric tube four times daily and/or
- Vancomycin 500 mg retention enema in 100 mL normal saline every 4-12 hours 1, 6
Note that intravenous vancomycin has no efficacy against CDI as it is not excreted into the colon 6, 7.
Surgical Consultation
Obtain prompt surgical evaluation if the patient develops:
- Perforation of the colon
- Toxic megacolon or severe ileus
- Serum lactate >5.0 mmol/L
- Systemic inflammation with deteriorating clinical condition despite antibiotic therapy 1, 5
Early surgical intervention reduces mortality, as outcomes worsen significantly with advanced disease 1.