Criteria & Principles
NOTE: Fidaxomicin will not require ID consult after 8/15/23. This is a costly medication and the patient’s ability to pay for complete course of therapy in outpatient setting must be assessed at the time of starting fidaxomicin. See details of how this will occur M-F, 8-5pm by clicking here.
- Discontinue antibiotics and proton-pump inhibitors (such as pantoprozole) as soon as clinically appropriate
- Review for laxative use in the last 24hrs
- Response assessment should be based on resolution of signs/symptoms, and NOT repeated PCR testing
- ID consult is recommended for management of fulminant or recurrent infection
- Preferred vancomycin preparation is the compounded oral capsules. Oral solution is reserved for those who cannot swallow capsules or require via tube.
- Oral administration of vancomycin is NOT systemically absorbed and should NOT replace IV vancomycin for treatment of concomitant systemic Gram-positive infections.
- Vancomycin IV should NOT be used to treat C. difficile infection.
Cost & Access Considerations
- Access to fidaxomicin in the outpatient setting may be cost-prohibitive. Patient’s ability to pay for complete course of therapy in the outpatient setting must be assessed at the time of starting fidaxomicin.
- Fecal microbiota transplantation (FMT) access may be subject to availability. Recommend Gastroenterology (GI) consultation to assess patient candidacy and clarify availability.
- Merck discontinued production of bezlotoxumab as of 1/31/25. DUHS has purchased extra doses; however, supply will be limited & likely eventually depleted in 2025-2026.
Treatment
Severity
All Severity
| Occurrence/Severity | Recommendations |
| First Occurrence |
Vancomycin 125mg PO QID for 10 days OR Fidaxomicin* 200mg PO BID for 10 days
Fidaxomicin should be considered for patients at increased risk of CDI recurrence (list not all-inclusive):
|
| Recurrent Episode |
If vancomycin was used for the initial episode: Vancomycin in tapered and pulsed regimenA OR Fidaxomicin* 200mg PO BID for 10 days If fidaxomicin was used for the initial episode: Vancomycin in tapered and pulsed regimenA If metronidazole was used for the initial episode: Vancomycin 125mg PO QID for 10 days OR fidaxomicin* 200mg PO BID for 10 days |
| Second or Subsequent Recurrent Episode |
Fidaxomicin* 200mg BID for 10 days OR Vancomycin in tapered and pulsed regimenA NOTE: if considering ambulatory fecal microbiota transplantation (FMT) for the prevention of recurrent CDI, consider placing an E-communication to Infectious Disease (ID) or ambulatory referral to GI. For urgent outpatient FMT questions please staff message Amy Barto, MD (medical director of the Duke FMT program). |
| Fulminant Disease |
Vancomycin: 500mg PO QID (If vancomycin unable to be given PO, use NG tube) AND Metronidazole 500mg IV Q8H If ileus is present: Consider adding vancomycin enema 500mg/100mL of normal saline Q6H For patients with fulminant CDI refractory to standard therapy: Recommend GI and ID consult. Consider fecal microbiota rectal suspension [REBYOTA]B administered via colonoscopy If FMT is performed for the treatment of fulminant CDI: 1. Anti-CDI antibiotics should be continued until pseudomembranes are no longer detected on colonoscopy and the patient has clinically improved following FMT (i.e. improvement in CDI-related symptoms, WBC, and CRP). 2. For subjects with pseudomembranes on colonoscopy after FMT, consider continuing anti-CDI antibiotics for 5 additional days after FMT. Longer durations may be required to bridge to eventual microbiome-based treatments (e.g. VOWST or REBYOTA enema) as an outpatient if symptoms are slow to resolve. Please note that colonoscopy-assisted FMT via Rebyota is not currently available for outpatients at Duke. 3. The optimal choice of anti-CDI antibiotic after FMT for fulminant CDI remains unknown; however, fidaxomicin may be preferred as vancomycin is more disruptive to the newly transplanted microbiota |
| C. difficile Prophylaxis: Agents for Use & Recommendations | |
| BezlotoxumabC |
Bezlotoxumab 10 mg/kg IV onceC as adjunctive therapy with active CDI treatment for patients at increased risk for CDI recurrence (i.e. age > 65 yrs, immunocompromised, severe CDI, and/or NAP1 strain) NOTE: Merck discontinued production of bezlotoxumab as of 1/31/25. DUHS has purchased extra doses, but supply will likely be depleted in 2025-2026. |
| Oral vancomycin prophylaxis (OVP) |
Dose: vancomycin PO 125 mg daily for secondary prophylaxis in select patients Duration: while receiving high-risk systemic antibiotics PLUS 5 days after antibiotic cessation
Evidence for efficacy of OVP remains limited and largely observational. Some studies have found benefit with OVP; however, this is not consistent across studies. Additionally, one case series found OVP may not reduce CDI incidence but rather just delay disease onset. One meta-analysis suggests no benefit when used as primary prophylaxis. Refer to Vancomycin (PO) | Duke CustomID for a detailed summary of available evidence. Clinicians may consider OVP for secondary prophylaxis in select individuals at high risk of recurrence (example cases below):
Oral vancomycin prophylaxis is NOT recommended for ANY of the following patient populations:
|
Diagnosis-Specific Information
ATapered and pulsed vancomycin regimen example: 125mg PO QID for 10-14 days, BID for 7 days, QD for 7 days, then every 2 or 3 days for 2-8 weeks.
BFecal microbiota rectal suspension [REBYOTA] is restricted to Gastroenterology (GI) or Infectious Diseases (ID) consult. Prior to use, REBYOTA must be thawed for ~24 hours.
CBezlotoxumab is restricted to ID or GI consult. Preferred as outpatient administration.
*Patient’s ability to pay for complete course of therapy in outpatient setting must be assessed at the time of starting fidaxomicin. Fidaxomicin should not be used for fulminant disease.
References
1. Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clinical Infectious Diseases. 2021;73(5):e1029-e1044.
2. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021;116(6):1124-1147.
3. Rao K, Zhao Q, Bell J, et al. An Open-Label, Randomized Trial Comparing Fidaxomicin with Oral Vancomycin for the Treatment of Clostridioides difficile infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections. Clin Infect Dis 2023; 78(2):277-282.
4. Mullane KM, Miller MA, Weiss K, et al. Efficacy of Fidaxomicin Versus Vancomycin as Therapy for Clostridium difficile Infection in Individuals Taking Concomitant Antibiotics for Other Concurrent Infections. Clin Infect Dis 2011;53(5):440-447.
5. Fitzpatrick F, Safdar N, Prehn J, Tschudin-Sutter S. How can patients with Clostridioides difficile infection on concomitant antibiotic treatment be best managed? Lancet Infect Dis 2022;22(11):e336-e340.
6. Alsoubani M, Chow JK, Rodday AM, et al. Comparative Effectiveness of Fidaxomicin vs Vancomycin in Populations with Immunocompromising Conditions for the Treatment of Clostridioides difficile Infection: A Single-Center Study. Open Forum Infect Dis 2024;11(1):ofad622.
7. Tariq R, Laguio-Vila M, Tahir MW, et al. Efficacy of oral vancomycin prophylaxis for prevention of Clostridioides difficile infection: A systematic review and meta-analysis. Therap Adv Gastroenterol 2021;14:1-11.