Version July 2025
| Clinical condition*¶ | Antibiotic treatment regimen | Adjunctive treatment |
| Initial episode (non-fulminant) |
For nonsevere disease*, if above agents are unavailable, metronidazole§ is a reasonable alternative (500 mg orally 3 times daily) | |
| Recurrent episodes (non-fulminant)¥ | ||
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| Following the antibiotic regimen, we refer these patients for traditional FMT◊◊. If an FMP is available and was not administered during prior recurrences, it is reasonable to administer a FMP** (eg, rectal suspension [Rebyota]ΔΔ, oral capsules [Vowst]¶¶) instead of traditional FMT after completion of CDI therapy. |
| Fulminant disease¶ (eg, hypotension or shock, ileus, megacolon) |
Reassess clinical status in 24 to 48 hours§§ | Assess all patients for indications for surgery. For patients with ileus, we also administer vancomycin rectally until ileus is resolved. |
CDI: Clostridioides difficile infection; FMP: fecal microbiota products; FMT: fecal microbiota transplantation; IV: intravenously.
* 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. Nonsevere disease is supported by a white blood cell count ≤15,000 cells/microL and serum creatinine level <1.5 mg/dL (or <50% rise from baseline creatinine level). Severe disease is supported by a white blood cell count >15,000 cells/microL and/or serum creatinine level ≥1.5 mg/dL (or ≥50% rise from baseline creatinine level). Fulminant disease is supported by presence of hypotension or shock, ileus, or megacolon.
¶ Patients with severe or fulminant CDI also warrant assessment for indications for surgery; refer to UpToDate topic on treatment of CDI for further discussion.
Δ For patients with nonfulminant disease, we typically suggest a fidaxomicin-based regimen over a vancomycin-based regimen. Use of fidaxomicin has been associated with a benefit with respect to CDI recurrence rates (10 to 15% decrease). In the setting of cost constraints, we prioritize use of fidaxomicin for patients at greatest risk for CDI recurrence (age ≥65 years, severe CDI, or immunosuppression). Vancomycin remains an acceptable agent for treatment of initial and recurrent CDI.
◊ 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.
§ 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.
¥ Recurrent CDI is defined by resolution of CDI symptoms while on appropriate therapy, followed by reappearance of symptoms within 2 months of discontinuing treatment.
‡ If fidaxomicin is not available, a tapered and pulsed vancomycin regimen or standard vancomycin regimen are both reasonable alternatives.
† A fidaxomicin regimen is also a reasonable alternative if oral vancomycin cannot be used.
** FMPs are fecal microbiota products that are approved by the United States Food & Drug Administration (FDA) for use in patients with recurrent CDI to prevent further recurrences. Two products exist: a rectal suspension (fecal microbiota live-jslm; Rebyota) and an oral capsule (fecal microbiota spore live-brpk; Vowst). The selection of the FMP depends on availability, cost considerations, and patient preferences. We avoid using FMPs in patients who are severely immunocompromised (eg, CD4 cell count <200 cells/microL or absolute neutrophil count <500 cells/microL) given the scarcity of safety data for this patient population.
¶¶ The oral capsule FMP formulation (Vowst) is administered as 4 capsules once daily on an empty stomach for 3 consecutive days, beginning 2 to 4 days after the last dose of antibiotics for CDI treatment. The first dose should be preceded by a bowel preparation according to the manufacturer's directions; refer to the UpToDate topic on treatment of CDI and prescribing information for further details on administration. Adverse effects are generally mild and include mild abdominal distension, fatigue, constipation, chills, and diarrhea.
ΔΔ The rectal enema FMP formulation (Rebyota) is administered as a one-time dose of 150 mL via the rectum. It should be administered 24 to 72 hours after the last dose of antibiotics for CDI treatment. Prior to being given, the enema needs to be thawed in the refrigerator for approximately 24 hours. Adverse effects are the same as those of any retention enema and include mild abdominal pain, distension, diarrhea, flatulence, and nausea.
◊◊ For patients who cannot undergo FMT (eg, lack of availability, immunocompromised host) or who relapse despite two FMTs (at least one of which was via colonoscopy), we suggest suppressive oral vancomycin (125 mg orally once daily). Duration of suppressive vancomycin is discussed in more detail in the UpToDate topic on treatment of CDI.
§§ Patients who are improving should continue the treatment for 10 to 14 days. Once the patient clinically improves, the IV metronidazole can be stopped and the vancomycin dose can be reduced to the standard dose used in non-fulminant disease. For patients who are not improving, details regarding further interventions are discussed in detail in the UpToDate topic on treatment of CDI.
