Clostridioides difficile Infection

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Site: 
UCSF Medical Center Mission Bay (Adult)
UCSF Medical Center Mount Zion
UCSF Medical Center Parnassus Heights
Modified Date: 
October 21, 2019
March 14, 2022
July 17, 2024
August 19, 2024
Category: 
Syndrome Specific Guidelines
Document: 
PDF icon CDI Adult Treatment Guideline_Updated 2024.pdf

 

UCSF Medical Center Adult Clostridioides difficile management guidelines

Quick Links:
Principles of CDI Management
Treatment of CDI in Adult Patients, Initial Episode
Treatment of CDI in Adult Patients, Recurrent Disease
Special Situations

INTRODUCTION

The Adult Clostridioides difficile management guideline establishes evidence-based standards for management of C. difficile infection (CDI) at UCSF Medical Center. The guideline has been adapted from published consensus guidelines from the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the American College of Gastroenterology (ACG) with input from the Antimicrobial Stewardship Program, the Infectious Diseases Management Program, and the Infectious Diseases division.

 

Date

Main changes

2024 update

Vowst® (fecal microbiota spores live-brpk) was added to UCSF formulary with inpatient adult restrictions for ID/ASP. The IDSA/SHEA guidelines have not yet addressed this agent, and ACG suggests use similar to current indications for FMT. This product is manufactured from human fecal matter sourced from qualified donors and is used to prevent the recurrence of CDI.

2022 update

Fidaxomicin is now first-line therapy for first and second C. difficile episodes (non-fulminant) Added recommendation for bezlotoxumab for certain patients after the 1st episode and all patients after the 2nd episode of CDI

Guidelines now apply only to UCSF Health (ZSFG and SFVA have independent guidelines)

 

DEFINITIONS

 

Abbreviation

Definition

ASP

Antimicrobial Stewardship Program (adult)

CDI

Clostridioides difficile infection

FMT

Fecal Microbiota Transplantation

ID

Infectious Diseases (adult)

GI

Gastroenterology

 

PRINCIPLES OF CDI MANAGEMENT

  • Refer to the Hospital Epidemiology and Infection Control website for information on work-up of diarrhea and guidance on Infection Control issues pertaining to CDI at UCSF Medical Center (http://infectioncontrol.ucsfmedicalcenter.org/ucsf-clostridium-difficile-infection-prevention)
  • Stop all unnecessary antibiotics, shorten antibiotic courses, and narrow the spectrum of antibiotic activity when possible
  • Stop acid suppressive medications, especially proton-pump inhibitors, when possible
  • Do not use anti-peristaltic agents until acute symptoms of CDI improve

 

TREATMENT OF CDI IN ADULT PATIENTS, INITIAL EPISODE

Clinical definition

Criteria

Treatment

Initial episode, non-complicated, toxin protein negative, toxin gene positive

 

Treatment for colonization typically is not necessary

If treating, most patients: Vancomycin 125 mg po q6h x 10 days

In symptomatic patients at very high risk for relapse (advanced age, severe immunocompromise, or need for ongoing systemic antibiotics) could consider Fidaxomicin 200 mg po twice daily x 10 days*

Initial CDI episode, non-complicated, toxin protein positive, toxin gene positive

Not meeting criteria for fulminant

Fidaxomicin 200 mg po twice daily x 10 days*

Alternative: Vancomycin 125 mg po q6h x 10 days

Secondary prophylaxis after initial episode after initial episode of toxin protein positive infection

Toxin protein positive, no history of heart failure AND meets one of the following:

  1. Hematologic cancer with neutropenia expected > 30 days
  2. Recent bone-marrow transplant or treatment for GVHD
  3. Solid-organ transplant < 3 months
  4. Otherwise not an FMT candidate

Treat for initial episode as above

Bezlotoxumab 10 mg/kg as a single dose if not previously administered

Fulminant

Hypotension, shock, ileus, and/or megacolon

Vancomycin 500 mg po/ng q6h + metronidazole 500 mg IV q8h +/- rectal vancomycin

Rectal vancomycin should be considered in patients with ileus. It is given as 500 mg in 100 mL of 0.9% NaCl and instilled q6h (retain each dose for 1h)

Consult ID and General Surgery for consideration of colectomy versus diverting loop ileostomy with colonic lavage

* can transition to po vancomycin for completion of course if unable to obtain outpatient. If insurance does not cover fidaxomicin can try the MERCK patient assistance program at www.merckhelps.com.

 

TREATMENT OF CDI IN ADULT PATIENTS, RECURRENT DISEASE

Recurrence is defined as the re-appearance of symptoms and signs of CDI within 8 weeks after completion of therapy for prior CDI episode for which symptoms and signs had resolved, and assumes toxin gene AND toxin protein positive in all instances.

Clinical definition

Criteria

Treatment

1st CDI recurrence (non-fulminant)

 

Fidaxomicin 200 mg po q12h x 10 days

Alternative:

Vancomycin taper:
125 mg po 4x daily x 14 days
125 mg po 2x daily x 7 days
125 mg po 1x daily x 7 days
125 mg po every other day x 8 days (4 doses)
125 mg po every 3 days x 2 weeks (5 doses)

Secondary prophylaxis after 1st recurrence

 

Treat for initial episode as above

Bezlotoxumab 10 mg/kg as a single dose if not previously administered

 

≥ 2 CDI recurrence (non-fulminant)

 

Vancomycin taper:

125 mg po 4x daily x 14 days
125 mg po 2x daily x 7 days
125 mg po 1x daily x 7 days
125 mg po every other day x 8 days (4 doses)
125 mg po every 3 days x 2 weeks (5 doses)

PLUS

Evaluate for secondary prophylaxis with fecal microbiota spores, live-brpk (Vowst®)  (alternative: fecal microbiota transplant (FMT))

Consult ID, GI

Secondary prophylaxis after ≥ 2nd CDI recurrence

 

Initiate fecal microbiota spores, live-brpk (Vowst®, 4 capsules po daily x 3 days) 2-4 days AFTER completing antibacterial treatment for recurrent CDI

Preferentially administer prior to consideration of FMT

 

SPECIAL SITUATIONS

Bezlotoxumab (see clinical criteria above)

  • Do not give in congestive heart failure
  • Treat for episode of C. difficile with fidaxomicin or oral vancomycin as above
  • Administer as an outpatient if possible
  • Criteria for inpatient administration: Must be expected to be hospitalized > 14 days after C. difficile episode
    • All use requires ID/ASP approval
    • This agent is not routinely stocked in inpatient pharmacy. Contact pharmacy purchasing team several days in advance to initiate order.
  • Only may receive one-time dose (not studied outside of this)

Fecal microbiota spores, live-brpk (see clinical criteria above)

  • Avoid concurrent use with antibacterials
  • Treat for episode of C. difficile with fidaxomicin or oral vancomycin as above
  • Administer as an outpatient if possible
  • Prior to administration of this biotherapeutic, the patient should drink 296 mL (10 oz) of magnesium citrate on the day before and at least 8 hours prior to taking the first dose of fecal microbiota spores, live-brpk
  • For patients with impaired renal function, the clinical study participants received polyethylene glycol electrolyte solution (250 mL)
  • Criteria for inpatient administration: Must be expected to be hospitalized > 14 days after C. difficile episode
  • All use requires ID/ASP approval
    • This agent is not routinely stocked in inpatient pharmacy. Contact pharmacy purchasing team several days in advance to initiate order.
    • Only may receive one course (currently not studied outside of this)
  • Avoid in patients with severe immunocompromise

Comment on probiotics

Mixed data exist regarding use of probiotics for primary prevention of CDI. There is insufficient data to support use for secondary prophylaxis. Can consider use based on patient and provider preference. Relatively contraindicated in immunocompromised populations.

Comment on duration of therapy in patients receiving ongoing antibiotics

Extension of CDI therapy in patients receiving ongoing systemic antibiotics is not routinely recommended. Can consider use based on patient and provider preference.

Comment on secondary antibiotic prophylaxis for CDI

Do not routinely use prophylaxis if treating with fidaxomicin as the benefit of this therapy is to preserve the microbiome.

Mixed data exist regarding use of vancomycin for secondary prevention of CDI. Can consider use based on patient and provider preference.

For patients with recurrent CDI who are not candidates for FMT, who relapsed after FMT x 2, or who require ongoing or frequent courses of antibiotics, suppressive oral vancomycin may be used to prevent further recurrences.

 

REFERENCES

  1. Carignan A, Poulin S, Martin P, et al. Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections. Am J Gastroenterol. 2016;111(12):1834-1840. doi:10.1038/ajg.2016.417
  2. Caroff DA, Menchaca JT, Zhang Z, et al. Oral vancomycin prophylaxis during systemic antibiotic exposure to prevent Clostridiodes difficile infection relapses. Infect Control Hosp Epidemiol. 2019;40(6):662-667. doi:10.1017/ice.2019.88
  3. Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55 Suppl 2(Suppl 2):S154-161. doi:10.1093/cid/cis462
  4. Feuerstadt P, Louie TJ, Lashner B, et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med. 2022;386(3):220-229. doi:10.1056/NEJMoa2106516
  5. 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. Clin Infect Dis. 2021;73(5):e1029-e1044. doi:10.1093/cid/ciab549
  6. Kelly CP, LaMont JT. Clostridium difficile--more difficult than ever. N Engl J Med. 2008;359(18):1932-1940. doi:10.1056/NEJMra0707500
  7. 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. doi:10.14309/ajg.0000000000001278
  8. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085
  9. Mullane KM, Winston DJ, Nooka A, et al. A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation. Clin Infect Dis. 2019;68(2):196-203. doi:10.1093/cid/ciy484
  10. Peery AF, Kelly CR, Kao D, et al. AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases. Gastroenterology. 2024;166(3):409-434. doi:10.1053/j.gastro.2024.01.008
  11. Sims MD, Khanna S, Feuerstadt P, et al. Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial. JAMA Netw Open. 2023;6(2):e2255758. doi:10.1001/jamanetworkopen.2022.55758
  12. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478-498; quiz 499. doi:10.1038/ajg.2013.4
  13. Van Hise NW, Bryant AM, Hennessey EK, Crannage AJ, Khoury JA, Manian FA. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016;63(5):651-653. doi:10.1093/cid/ciw401
  14. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med. 2017;376(4):305-317. doi:10.1056/NEJMoa1602615

 

Original guideline prepared by:

UCSFMC: Sarah Doernberg, MD, MAS; Catherine Liu, MD; Jennifer Babik, MD, PhD; Rachel Wattier, MD; Alexandra Hilt-Horeczko, PharmD; Jonathan Faldasz, PharmD
SFVA team: Harry Lampiris, MD; Daniel Maddix, PharmD
ZSFG team: Lisa Winston, MD; Gregory Melcher, MD; Camille Beauduy, PharmD

2019 revision prepared by:

UCSFMC: Sarah Doernberg, MD, MAS
SFVA: Jennifer Mulliken, MD; Sean Chow, PharmD ZSFG: Lisa Winston, MD; Camille Beauduy, PharmD

2022 revision prepared by:

Ripal Jariwala, PharmD
Sarah Doernberg, MD, MAS

2024 revision prepared by:

Ripal Jariwala, PharmD, BCIDP
Emily Kaip, PharmD, BCIDP, BCPS
Will Simmons, MD
Sarah Doernberg, MD, MAS

Approved by:

Group

Date

IDMP

2.29.16

Clinical ID group at VAMC

2.29.16

Clinical ID group at ZSFG

2.29.16

Trihospital group meeting

8.19.19

IDMP

9.10.19

IDMP

08.10.21

UCSF P&T

02.09.22

UCSF Antimicrobial Subcommittee

05.13.24

UCSF P&T

08.19.24