Version July 2025
CDI: Clostridium difficile infection; FMP: fecal microbiota product; FMT: fecal microbiota transplant; IV: intravenous.
* The criteria proposed for defining severe or fulminant CDI are based on expert opinion and may need to be reviewed upon publication of prospectively validated severity scores for patients with CDI. Patients with severe or fulminant CDI also warrant assessment for indications for surgery; refer to UpToDate topic on treatment of CDI for further discussion.
¶ Systemic absorption of enteral vancomycin can occur in patients with mucosal disruption due to severe or fulminant colitis; this consideration is particularly important for patients with kidney insufficiency (creatinine clearance <10 mL/minute). Therefore, in patients with severe or fulminant colitis and renal insufficiency (creatinine clearance <10 mL/minute) who are receiving a prolonged course (>10 days) of enteral vancomycin therapy, we suggest monitoring serum vancomycin levels unless the patient is on dialysis.
Δ Rectal vancomycin is administered as a retention enema in addition to oral vancomycin.
◊ Response to treatment should be reassessed in 24 to 48 hours. For patients improving on therapy, we continue therapy for the usual duration of therapy (10 days). Once the patient clinically improves, the metronidazole can be stopped and the vancomycin dose can be reduced to the standard dose used in non-fulminant disease. Patients who have no sustained improvement in vital signs after 24 to 48 hours should be considered for further intervention (eg, surgery).
§ For patients with nonfulminant disease, we suggest a fidaxomicin-based regimen over a vancomycin-based regimen. Vancomycin remains an acceptable agent for treatment of initial and recurrent CDI. In the setting of cost constraints, we prioritize fidaxomicin for patients at greatest risk for CDI recurrence (age ≥65 years, severe CDI, or immunosuppression).
¥ If fidaxomicin and vancomycin are both not available, metronidazole is an alternative option in non-severe CDI. Metronidazole should be avoided in patients who are frail, age ≥65 years, or who develop CDI in association with inflammatory bowel disease. Caution is also warranted during pregnancy and lactation.
‡ If fidaxomicin is not available, a tapered and pulsed vancomycin regimen or standard vancomycin regimen are both reasonable alternatives.
† A fidaxomicin regimen (200 mg orally twice daily for 10 days) is also a reasonable alternative if oral vancomycin cannot be used.
** Fecal microbiota products (FMPs) include a rectal suspension (Rebyota) or an oral capsule (Vowst). Selection of which product to use depends on availability, cost considerations, and patient preferences. We avoid using FMPs in patients who are immunocompromised given the scarcity of safety data for this patient population. Adjunctive FMP is initiated several days after completion of CDI therapy. For details of timing, dose, and method of administration, refer to UpToDate topic and Lexidrug monographs for fecal microbiota oral capsules or oral suspension.
¶¶ In contrast to the above approach, some favor FMT for patients who have received antibiotic treatment for at least two CDI episodes (ie, initial episode plus one recurrence), who subsequently present with a third or further CDI episode (second or subsequent recurrence).
ΔΔ If an FMP is available and was not administered during the prior recurrence, it is reasonable to administer it (eg, rectal suspension or oral capsule) instead of traditional FMT after completion of CDI therapy.
