Guideline Vs Reality: Survey of Clinician Preferences in the Management of Clostridioides difficile Infection in Adults Highlights Barriers to Optimal Care

Kendall Bell, PharmD, BCIDP

Image credits: Beth Israel Deaconess Medical Center (BIDMC), Boston, MA

Clostridioides difficile infection (CDI), one of the most common health care–acquired infections, is associated with significant morbidity, mortality, and risk of recurrence. The CDC classified CDI as an urgent threat in the 2019 Antibiotic Resistance Threats Report.¹ The 2022 update indicated a decrease in CDI cases in the years for which data were available, but the 2024 Resistance Threats report omitted CDI so the trend in the past 5 years is not well known.^2,3 Recently, the CDI landscape has benefited from updated guidelines and approvals of 2 live biotherapeutic products, but there is still heterogeneity in the use and availability of various treatments.⁴

CDI management requires knowledge of not only clinical trials and outcomes data, but also formulary restrictions, product availability, and cost. As a result, treatment decisions made by excellent clinicians may sometimes be guideline discordant. An observational study published in 2024 compared fidaxomicin use before and after the 2021 focused guideline update from the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America, which recommended fidaxomicin over oral vancomycin for initial and recurrent CDI.⁵ Although its use modestly increased, the authors concluded this agent was still underutilized and use varied by hospital location and size. A recent survey of infectious disease (ID) clinicians published in Open Forum Infectious Diseases inquired further about CDI treatment preferences and barriers.⁴

The survey was distributed to members of the IDSA Emerging Infections Network (EIN) via 3 separate emails in May 2024. The survey included physicians, pharmacists, and advanced practice providers practicing in adult infectious diseases. The survey collected demographic information about respondents and the number of patients with CDI they had treated in the past year. Subsequent questions asked about usual practice, preferred treatment regardless of formulary or financial concerns, institutional guideline recommendations, and other situations. The results were analyzed using descriptive statistics.

Of the 1618 EIN members, 577 completed the survey, yielding a response rate of 36%. Nearly 90% were ID physicians, with the rest being other health care professionals. The practice settings of respondents varied, with the most common being university hospitals, non-university teaching hospitals, and community hospitals. Those who responded had a significant amount of experience, with over 80% reporting at least 5 years of experience after terminal ID training and about 65% reporting treating over 10 patients with CDI in the last year.

10D, for 10 days; CDI, Clostridioides difficile infection; Ext, extended-pulsed fidaxomicin dosing regimen; IDSA, Infectious Diseases Society of America; PO, by mouth; PT, pulsed-tapered vancomycin dosing regimen; SHEA, Society for Healthcare Epidemiology of America.

Table 1 describes some key survey findings alongside guideline recommendations. When asked about their institutional guidelines, 72% of respondents selected enteral vancomycin as first line for initial, nonfulminant CDI (but in some cases, local guidelines stratified choice of treatment by risk factors). Another question asked which patient characteristics influence clinicians to select fidaxomicin over other agents for nonfulminant CDI. Answers selected by over 50% of respondents were recurrent CDI, immunocompromised state, and age over 65 years. The most common barrier to prescribing fidaxomicin was outpatient insurance coverage issues (selected by 82%), followed by inpatient formulary or cost restrictions (47%).

The survey also inquired about alternative agents, including bezlotoxumab and fecal microbiota transplantation (FMT). About three-quarters of respondents indicated having access to bezlotoxumab, a number which has likely decreased following the announcement of this drug’s discontinuation in early 2025.⁸ Just under 50% of respondents reported availability of FMT using donor stool in their practice, while 36% and 30% reported access to fecal microbiota live-jslm (Rebyota) and fecal microbiota spores live-brpk (Vowst), respectively. The COVID-19 pandemic, the FDA’s changing policies around FMT, and high costs contribute to limited access to these therapeutics.

This study’s strengths include the large number of participants surveyed, the breadth of topics covered, and the focus on barriers that clinicians face in CDI management. Some limitations should be acknowledged, including sampling bias. Individuals with the most interest in CDI were possibly more likely to respond, and since the EIN subscribers did not include members of other relevant specialties, such as gastroenterology, these perspectives were not captured. This survey’s results reflect the time when it was distributed, prior to events in the last year that have impacted access to specific therapeutics. The results highlight the challenges clinicians face while navigating financial approvals, inpatient and outpatient formulary restrictions, and product availability. Future cost-effectiveness studies and additional investigations into clinician perspectives, such as this one, can continue to help unite real-life practice and guidelines.

References

1. CDC. Antibiotic Resistance Threats in the United States, 2019. 2019. Revised December 2019. Accessed September 19, 2025. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/2019-ar-threats-report-508.pdf

2. CDC. COVID-19: US Impact on Antimicrobial Resistance, 2022 Special Report. 2022. Accessed September 19, 2025. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/covid19-impact-report-508.pdf

3. CDC. Antimicrobial Resistance Threats in the United States, 2021-2022. 2024. Accessed September 19, 2025. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/antimicrobial-resistance-threats-update-2022-508.pdf

4. Boton N, Patel PK, Beekmann SE, et al. Clinician management preferences for Clostridioides difficile infection in adults: a 2024 Emerging Infections Network Survey. Open Forum Infect Dis. 2025;12(7):ofaf335. doi:10.1093/ofid/ofaf335

5. Dubberke ER, Li Q, Obi EN, Turzhitsky V, Siddiqui F, Nathanson BH. A retrospective assessment of guideline adherence and treatment outcomes from Clostridioides difficile infection following the IDSA 2021 clinical guideline update: Clostridioides difficile infection. Open Forum Infect Dis. 2024;11(10):ofae524. doi:10.1093/ofid/ofae524

6. 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

7. Kelly CR,Fischer M, Allegretti J, 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. Drug shortages: bezlotoxumab injection. US Food and Drug Administration. December 23, 2024. Accessed July 19, 2025. https://dps.fda.gov/drugshortages/discontinuations/bezlotoxumab-injection.