Pharmacists Are Key Players in C difficile Infection Prevention

Clostridioides difficile (C difficile) infection (CDI) is estimated to affect more than 450,000 patients in the US annually, resulting in significant morbidity and mortality for patients, and substantial financial burden to health care institutions.¹ C difficile, a gram-positive, anaerobic, spore-forming bacillus, is spread via the fecal to oral route. Without proper sanitation or contact precautions, spores can persist on health care equipment and surfaces for month, leading to pathogen transmission.² Common risk factors for CDI include older age, antibiotic exposure, hospitalization, proton pump inhibitor use, immunosuppression, and history of CDI.^2,3

As one of the most common health care-associated infections, CDI is labeled as an urgent public health threat by the CDC.⁴ While appropriate treatment is imperative, the prevention of CDI—both initial and recurrent infections—is pivotal to patient outcomes and public health.

Pharmacist’s Role in Preventing CDI

Image credit: syahrir | stock.adobe.com

It takes a village to prevent CDI, including pharmacists. Of the CDC’s essential practices for CDI prevention, pharmacists play a vital role in antimicrobial stewardship (AMS).¹ Pharmacists are often co-leaders of hospital AMS programs and spearhead initiatives to optimize antimicrobial use, including publishing local treatment guidelines, implementing antimicrobial restriction criteria, conducting allergy assessments, and performing prospective audit and feedback.^5,6 These initiatives may reduce CDI through optimization of antibiotic exposure, which is the most common modifiable risk factor.⁷

While antimicrobial therapy is often necessary, the connection between suboptimal antimicrobial therapy and CDI is clear. A recent study found that patients initiated on antimicrobial treatment for asymptomatic bacteriuria (ASB) in the emergency department had an increased length of hospitalization (mean: 5.1 days vs 4.2 days, 95% CI 1.08-1.23) and rate of CDI (0.9% vs 0%, p = .02) compared with patients who did not receive therapy.⁸ Additionally, a large, matched cohort study found that patients with penicillin allergies had an approximate 26% increased risk of CDI compared with those who did not have penicillin allergies, attributed to receiving alternative antibiotics, including clindamycin and fluoroquinolones.⁹ These studies highlight the importance of AMS initiatives such as local guidance on urinary tract infections/ASB and allergy assessments to ensure optimal antimicrobial therapy.

Although a singular initiative alone may not prevent CDI, a combination of AMS initiatives can lead to substantial reduction. A recent study described the impact of pharmacist-led initiatives on health care-associated CDI rates, including the creation of an antibiotic guideline book, beta-lactam allergy education, penicillin-skin testing, and prospective audit of fluoroquinolone use. This retrospective assessment found an 81% reduction in health care facility onset CDI after initiative implementation.¹⁰ While it’s important to highlight the impact of specific AMS initiatives, every pharmacist within the hospital or community can play a role in CDI prevention through ensuring patients receive optimized antimicrobial therapy.

Fecal Microbiota Transplant – Preventing Recurrent CDI

Strategies for CDI prevention extend well beyond AMS. For patients with a history of initial CDI, 15% to 30% will experience a recurrent episode, and of those with a first recurrence, 40% will experience a second. Infection recurrence occurs regardless of appropriate treatment, leading to poor patient outcomes and high health care costs.^11,12 While many strategies may be implemented to reduce CDI, fecal microbiota transplant (FMT) may be an option for patients with recurrent infection. 

FMT is a preventative strategy for recurrent CDI, specifically recommended by the Infectious Diseases Society of America for patients with a second or subsequent CDI recurrence.¹³ Historically, FMT involved the transfer of healthy donor stool to the affected patient via upper gastrointestinal (via an oral, nasogastric/nasojejunal tube, such as an endoscopy) and lower gastrointestinal (such as a colonoscopy, sigmoidoscopy, or an enema) administration. Unlike conventional CDI therapies, FMT restores the gastrointestinal microbiome, thereby preventing further infection.^14,15

Over the last few years, 2 FDA-approved therapeutics have become available: fecal microbiota spores, live-brpk (Vowst; Nestle HealthScience, Seres Therapeutics) and fecal microbiota, live-jslm (Rebyota; Ferring Pharmaceuticals). With increased accessibility of FMT products, pharmacists’ knowledge of such agents is essential. Pharmacists can advocate for FMT when appropriate, assist with formulary addition and acquisition, and perform patient counseling.

Vowst is an oral FMT option for patients with recurrent CDI, administered as a 3-day course beginning 2 to 4 days after completion of CDI treatment. Mechanistically, Vowst is composed of live bacterial spores, which inhibit C difficile germination and restore the gastrointestinal microbiome.¹⁶ The ECOSPOR III (NCT03183128) trial found that Vowst significantly reduced recurrence at week 8 compared with placebo, regardless of patient age or anti-CDI antibiotic exposure (12% vs 40%, respectively; RR: 0.32, 95% CI 0.18-0.58). Recurrence rates at 24 weeks were about 21.3% in the treatment cohort and 47.3% in the placebo cohort, exhibiting sustained response.^17,18 Additionally, the ECOSPOR IV trial (NCT03183141) demonstrated similar results in patients receiving Vowst, with 8.7% and 13.7% of patients experiencing recurrence at 8 weeks and 24 weeks, respectfully.¹⁹ Vowst has been found to be well-tolerated with common mild gastrointestinal adverse effects (AEs).^17-19

Rebyota is a rectally-administered FMT option for patients with recurrent CDI, given 1 to 3 days after completion of CDI treatment. This 150 mL rectal suspension is administered by a trained health care processional and must be thawed prior to use.²⁰ Aimed to restore gastrointestinal eubiosis, Rebyota has been found to significantly improve treatment success (defined as absence of CDI) within 8 weeks when compared with placebo (70.6% vs 57.5%, respectively).²¹ Similar results were reproduced in PUNCH CD3-OLS (NCT03931941), a phase 3 prospective observational cohort study, which found approximately 73.8% of patients had treatment success at 8 weeks and 91% sustained clinical response at 6 months in those with initial treatment success. Rebyota is well-tolerated, with common mild AEs including abdominal pain, diarrhea, flatulence, and nausea.²²

Conclusion

CDI is an urgent public health threat, warranting a focus on not only appropriate treatment, but prevention. While prevention of CDI requires an interdisciplinary effort, pharmacists are well-positioned to intervene. Pharmacists play a pivotal role in CDI prevention through the implementation of formal AMS initiatives, recommendations for antimicrobial optimization, and advocacy for the appropriate use of new FMT therapies. 

REFERENCES

1. Kociolek L, Gerding D, Carrico R, et al. Strategies to prevent Clostridioides difficile infections in acute-care hospitals: 2022 update. Infect Control Hosp Epidemiol. 2023;44(4):527-549. doi:10.1017/ice.2023.18

2. Czepiel J, Drozdz M, Pituch H, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2010;38(7):1211-1221. doi:10.1007/s10096-019-03539-6

3. Eeuwijk J, Ferreira G, Yarzabal J, et al. A systematic literature review on risk factors for and timing of Clostridioides difficile infection in the United States. Infect Dis Ther. 2024;13:273-298. doi:10.1007/s40121-024-00919-0

4. 2019 Antibiotic Resistance Threats Report. Centers for Disease Control and Prevention. Updated July 16, 2024. Accessed January 16, 2025. https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html.

5. Core Elements of Hospital Antibiotic Stewardship Programs. Centers for Disease Control and Prevention. Updated December 5, 2024. Accessed January 16, 2025. https://www.cdc.gov/antibiotic-use/hcp/core-elements/hospital.html

6. Barlam T, Cosgrove S, Abbo L, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of American and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-e77. doi:10.1093/cid/ciw118

7. Wenzler E, Mulugeta S, and Danziger L. The antimicrobial stewardship approach to combating Clostridium difficile. Antibiotics. 2015;4(2):198-215. doi:10.3390/antibiotics4020198

8. Petty L, Vaughn V, Flanders S, et al. Assessment of testing and treatment of asymptomatic bacteriuria initiated in the emergency department. Open Forum Infect Dis. 2020;7(12):ofaa527. doi:10.1093/ofid/ofaa537

9. Blumenthal K, Lu N, Zhang Y, et al. Risk of methicillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018;361:k2400. doi:10.1136/bmj.k2400

10. Gillespie L, Marzuq Y, Thomas A, Bunch C. Impact of pharmacist-led initiatives on healthcare-associated Clostridioides difficile rates. Pharmacy Practice in Focus: Health Systems. 2024;13(2):22-28.

11. Song J and Kim Y. Recurrent Clostridium difficile infection: risk factors, treatment, and prevention. Gut Liver. 2018;13(1):16-24. doi:10.5009/gnl18071

12. Guh A, Li R, Korhonen L, et al. Characteristics of patients with initial Clostridioides difficile infection that are associated with increased risk of multiple CDI recurrences. Open Forum Infect Dis. 2024;11(4):ofae127. doi:10.1093/ofid/ofae127

13. 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

14. Gough E, Shaikh H, Manges A. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994-1002. doi:10.1093/cid/cir632