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Journal of the Association of Medical Microbiology and Infectious Disease Canada logoLink to Journal of the Association of Medical Microbiology and Infectious Disease Canada
. 2026 Feb 11;11(1):37–50. doi: 10.3138/jammi-2025-0014

Diagnosis, treatment, and prophylaxis of Clostridioides difficile infections: A cross-sectional survey of Canadian clinicians

Connor Prosty 1,2,✉, Bennet Desormeau 1, Todd C Lee 2,3,4,*, Emily G McDonald 2,4,5,*
PMCID: PMC13167151  PMID: 42131376

Abstract

Background:

A recent international survey of clinician practices in the management of Clostridioides difficile infections (CDIs) identified numerous areas of practice heterogeneity. The degree of practice variability within Canada is unknown.

Methods:

Data from Canadian participants of an international survey of clinician CDI practices were extracted. Practice alignment with the Association of Medical Microbiology and Infectious Disease (AMMI) Canada CDI treatment guidelines was assessed. CDI practices were compared across provinces using the Fisher exact test with a simulated P value.

Results:

A total of 112 responses were obtained from eight provinces. Vancomycin (85.3% for first episode), vancomycin pulse and taper (P-T) (61.8% and 32.4% for first and second recurrences, respectively), and fecal microbiota transplant (32.4% for third recurrence) were preferred treatment strategies. Practice alignment with the AMMI Canada CDI guidelines for the treatment of recurrences was low (range 23.5%–32.4%, depending on the recurrence number). With respect to secondary CDI prophylaxis during antibiotic reexposure, there were interprovincial differences in the perceived indication (P = .03), whether to prescribe at all (P < .001), and duration of prophylaxis (P = .004). There was significant clinician support (>50%) for randomized clinical trials testing treatment strategies for recurrent episodes and for secondary prophylaxis.

Conclusion:

Despite the availability of national guidelines, we found significant heterogeneity in practice across Canada, often not aligned with guideline recommendations. These findings underscore the need for a platform trial comparing treatment strategies and a trial to establish the efficacy of secondary prophylaxis.

Keywords: Clostridioides difficile, fidaxomicin, prophylaxis, treatment, vancomycin

Lay Summary

Clostridioides difficile (also known as C. diff) is a bacterium that can infect the colon and cause severe diarrhea. It most commonly occurs after antibiotic use. C. difficile infections are one of the leading hospital-acquired infections in Canada and cost the health care system approximately 300 million dollars yearly. Even though national treatment guidelines exist in Canada to guide health care practitioners in the treatment of C. difficile, it is unclear how closely these are followed in everyday practice. Furthermore, a recent international survey of health care practitioners who regularly treat C. difficile demonstrated that its treatment differs greatly based on geographic location. To explore this, we analyzed over 100 responses from Canadian health care practitioners who treat C. difficile. We found that less than half of clinicians followed recommendations for treating recurrent C. difficile (ie, C. difficile that returns after treatment). Also, the use of medications to prevent recurrent C. difficile (ie, prophylaxis) was very different across provinces. Nevertheless, these practitioners strongly supported clinical trials in multiple areas of C. difficile care. These findings highlight many areas where practices differ, and clinical trials may be helpful to create a consistent standard of care across Canada.

Introduction

Clostridioides difficile is an important cause of hospital-acquired and antibiotic-associated diarrhea worldwide (1). Approximately 38,000 cases of C. difficile infection (CDI) occur in Canada annually, 27% of which are recurrences (2). In Canada, recently, the prevalence of nosocomial CDI has been decreasing; however, the number of community-acquired cases has been rising (3,4). CDI places a significant burden on the Canadian health care system, with an attributable cost of $280 million yearly, primarily due to prolonged hospitalization (2).

Likely due to a well-established history of use, safety, and lower drug cost, vancomycin has been the most utilized therapy for CDI in many countries, including Canada (5). While there are other commercially available therapeutic options for CDI, including fidaxomicin (6) or microbiota-targeted therapies (7,8), uptake is limited due to cost and accessibility (9). Guidelines, including those from the Association of Medical Microbiology and Infectious Disease (AMMI) Canada, conflict on the application and positioning of these therapies and on other aspects of CDI clinical practice (5,10–12). This has contributed to considerable practice heterogeneity globally (13). It is unclear whether similar practice heterogeneity exists within Canada. Understanding Canadian practice, evaluating the availability and funding of CDI treatments, and assessing practice alignment with the AMMI Canada guidelines may reveal knowledge gaps. We therefore aimed to better characterize these gaps by analyzing the subset of Canadian data from our international CDI practice survey (13).

Methods

Design

This study was approved by the McGill University Health Centre Research Ethics Board (2025-10917). The design of the survey has been described elsewhere (13). Briefly, the survey was structured in two sections. The first section collected demographics and posed questions surrounding the use of secondary CDI prophylaxis during antibiotic re-exposure. The second section asked questions surrounding diagnostic testing, CDI treatment preferences, and questions about the availability and funding of CDI therapies by province. The sections were administered consecutively with an opt-out option in between so as to maximize responses to the first section.

Eligibility

Attending physicians in any specialty, fellows in infectious disease or medical microbiology, and infectious disease pharmacists who had treated three or more cases of CDI in adults in the past year were eligible to participate.

Distribution

The survey, available in English or French, was administered via REDCap and disseminated online by X (formerly Twitter), email, and society listservs (including AMMI Canada). Responses were collected from September 19, 2024, to December 1, 2024.

Statistical analyses

The subset of participants from Canada was analyzed post hoc. Nonsensical, identical, or straightlined responses were removed. Responses were grouped according to province/territory. We grouped the responses from Atlantic Canada to preserve respondent confidentiality because there were fewer than two responses from several provinces. Availability and funding of CDI therapies and practice alignment with the AMMI Canada guideline recommendations (5) were presented as proportions. CDI diagnostics, treatments, and secondary prophylaxis practices were compared across all provinces by the Fisher exact test using Monte Carlo simulations with 10,000 iterations due to small sample sizes and the use of multiple categories (14). There was no adjustment for multiple hypothesis testing given the exploratory nature of the analyses. A geographic depiction of responses was rendered using ggplot2 (15). RAWGraphs 2.0 (16) was used to generate alluvial diagrams for treatment selections. R (Version 4.3.2; R Foundation for Statistical Computing, Vienna, Austria) was used for all analyses.

Results

Demographics

There were 112 eligible Canadian responses from a total of 119 (94.1%); the remaining 7 were excluded because only demographic questions were answered. Responses originated from eight provinces/regions, including Quebec (42.0%), Ontario (30.4%), British Columbia (12.5%), Alberta (7.1%), Manitoba (3.6%), Saskatchewan (1.8%), and Atlantic Canada (2.7%) (Figure 1, Table 1). The majority of participants were attending physicians (89.3%), and most specialized in infectious diseases/medical microbiology (60.7%) or general internal medicine (24.1%). Most respondents practised at a university centre (64.3%) and spent ≤25% of their working hours on research (83.9%). Most respondents (51.8%) had managed 3 to 10 cases of CDI in the preceding year, and 48.2% had >10 cases.

Figure 1: Geographic distribution of respondents.

Figure 1:

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Table 1:

Demographic data

Characteristic Alberta;n = 8 (7.1%) British Columbia;n = 14 (12.5%) Manitoba;n = 4 (3.6%) Atlantic Canada;n = 3 (2.7%) Ontario;n = 34 (30.4%) Quebec;n = 47 (42.0%) Saskatchewan;n = 2 (1.8%) Total;N = 112
Training
 Attending 7 (87.5) 13 (92.9) 2 (50) 3 (100) 31 (91.2) 42 (89.4) 2 (100) 100 (89.3)
 Infectious disease pharmacist 1 (12.5) 1 (7.1) 0 (0.0) 0 (0.0) 2 (5.9) 1 (2.1) 0 (0.0) 5 (4.5)
 Infectious disease/medical microbiology fellow 0 (0.0) 0 (0.0) 2 (50) 0 (0.0) 1 (2.9) 4 (8.5) 0 (0.0) 7 (6.2)
Cases of CDI managed in the last year
 3 to 10 4 (50) 3 (21.4) 3 (75) 1 (33.3) 12 (35.3) 34 (72.3) 1 (50) 58 (51.8)
 >10 4 (50) 11 (78.6) 1 (25) 2 (66.7) 22 (64.7) 13 (27.7) 1 (50) 54 (48.2)
Medical specialty
 Pharmacist 1 (12.5) 1 (7.1) 0 (0.0) 0 (0.0) 2 (5.9) 1 (2.1) 0 (0.0) 5 (4.5)
 Gastroenterology 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.9) 0 (0.0) 0 (0.0) 1 (0.9)
 General internal medicine 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (14.7) 22 (46.8) 0 (0.0) 27 (24.1)
 Infectious diseases 6 (75) 9 (64.3) 4 (100) 2 (66.7) 22 (64.7) 15 (31.9) 2 (100) 60 (53.6)
 Intensive care 0 (0.0) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 7 (14.9) 0 (0.0) 8 (7.1)
 Medical microbiology 0 (0.0) 3 (21.4) 0 (0.0) 1 (33.3) 2 (5.9) 2 (4.3) 0 (0.0) 8 (7.1)
 Other internal medicine subspecialty 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 2 (5.9) 0 (0.0) 0 (0.0) 3 (2.7)
Year of practice as an attending
 NA (ie, fellow or pharmacist) 1 (12.5) 1 (7.1) 2 (50) 0 (0.0) 3 (8.8) 5 (10.6) 0 (0.0) 12 (10.7)
 0–5 years 1 (12.5) 3 (21.4) 1 (25) 0 (0.0) 12 (35.3) 15 (31.9) 0 (0.0) 32 (28.6)
 11–20 years 2 (25) 1 (7.1) 1 (25) 0 (0.0) 10 (29.4) 14 (29.8) 1 (50) 29 (25.9)
 6–10 years 0 (0.0) 6 (42.9) 0 (0.0) 2 (66.7) 3 (8.8) 8 (17) 0 (0.0) 19 (17)
 >20 years 4 (50) 3 (21.4) 0 (0.0) 1 (33.3) 6 (17.6) 5 (10.6) 1 (50) 20 (17.9)
Practice setting
 Community hospital 0 (0.0) 9 (64.3) 1 (25) 0 (0.0) 13 (38.2) 17 (36.2) 0 (0.0) 40 (35.7)
 University hospital 8 (100) 5 (35.7) 3 (75) 3 (100) 21 (61.8) 30 (63.8) 2 (100) 72 (64.3)
Proportion of time spent on research
 0% (ie, none) 0 (0.0) 8 (57.1) 1 (25) 0 (0.0) 6 (17.6) 21 (44.7) 1 (50) 37 (33)
 1%–25% 7 (87.5) 5 (35.7) 3 (75) 2 (66.7) 19 (55.9) 20 (42.6) 1 (50) 57 (50.9)
 26%–50% 1 (12.5) 1 (7.1) 0 (0.0) 1 (33.3) 5 (14.7) 3 (6.4) 0 (0.0) 11 (9.8)
 51%–75% 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (8.8) 3 (6.4) 0 (0.0) 6 (5.4)
 >75% 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.9) 0 (0.0) 0 (0.0) 1 (0.9)
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CDI = Clostridioides difficile infection; NA = Not applicable

CDI diagnostics

A total of 71 (63.3%) participants responded to the diagnostics and treatments section of the survey (Table 2). Two-step diagnostic algorithms were more commonly used than one-step algorithms (66.2% versus 33.8%). The most frequently used first (or only) assay used was a nucleic acid amplification test (NAAT, 43.7%). There were no significant differences across provinces in diagnostic algorithms. Among respondents whose institutions used both toxin enzyme immunoassay (EIA) and NAAT (49 respondents), 14.3% reported never treating patients with discordant results (eg, NAAT+/toxin EIA–), 12.2% reported always treating, and the remaining 73.5% treated them contextually (Table 2).

Table 2:

CDI diagnostics and definitions of recurrence

Characteristic Alberta;n = 4 (5.6%) British Columbia;n = 6 (8.5%) Manitoba;n = 3 (4.2%) Atlantic Canada;n = 3 (4.2%) Ontario;n = 25 (35.2%) Quebec;n = 28 (39.4%) Saskatchewan;n = 2 (2.8%) Total;N = 71 P value
Number of steps in the diagnostic algorithm
 One step 0 (0.0) 0 (0.0) 0 (0.0) 1 (33.3) 14 (56.0) 9 (32.1) 0 (0.0) 24 (33.8) .56
 Two steps 4 (100.0) 6 (100.0) 3 (100.0) 2 (66.7) 11 (44.0) 19 (67.9) 2 (100.0) 47 (66.2)
Step 1 assay(s)
 GDH 1 (25) 0 (0.0) 1 (33.3) 2 (66.7) 4 (16.0) 1 (3.6) 0 (0.0) 9 (12.7) .57
 GDH + NAAT 0 (0.0) 1 (16.7) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (2.8)
 GDH + toxin EIA 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (8.0) 4 (14.3) 1 (50.0) 7 (9.9)
 NAAT 2 (50) 5 (83.3) 0 (0.0) 1 (33.3) 13 (52.0) 9 (32.1) 1 (50.0) 31 (43.7)
 NAAT + toxin EIA 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (7.1) 0 (0.0) 2 (2.8)
 Toxin EIA 1 (25) 0 (0.0) 1 (33.3) 0 (0.0) 3 (12.0) 3 (10.7) 0 (0.0) 8 (11.3)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (12.0) 9 (32.1) 0 (0.0) 12 (16.9)
Step 2 assay(s)*
 GDH 2 (50) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (4.3) .24
 GDH + NAAT 1 (25) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.1)
 NAAT 1 (25) 0 (0.0) 1 (33.3) 2 (100) 6 (54.5) 8 (42.1) 1 (50.0) 19 (40.4)
 NAAT + toxigenic culture/CCNA 0 (0.0) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.1)
 Toxin EIA 0 (0.0) 6 (100.0) 1 (33.3) 0 (0.0) 3 (27.3) 3 (15.8) 1 (50.0) 14 (29.8)
 Toxin EIA + toxigenic culture/CCNA 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (5.3) 0 (0.0) 1 (2.1)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (18.2) 7 (36.8) 0 (0.0) 9 (19.1)
How often NAAT+/toxin EIA– patients are treated for CDI†
 0% 1 (25) 0 (0.0) 0 (0.0) 1 (33.3) 2 (9.1) 2 (9.5) 1 (50.0) 7 (11.5) .93
 1%–25% 1 (25) 3 (50) 0 (0.0) 1 (33.3) 3 (13.6) 5 (23.8) 0 (0.0) 13 (21.3)
 26%–50% 0 (0.0) 2 (33.3) 0 (0.0) 0 (0.0) 1 (4.5) 2 (9.5) 0 (0.0) 5 (8.2)
 51%–75% 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 4 (18.2) 1 (4.8) 0 (0.0) 6 (9.8)
 76%–99% 2 (50) 0 (0.0) 1 (33.3) 0 (0.0) 3 (13.6) 3 (14.3) 0 (0.0) 9 (14.8)
 100% 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (9.1) 3 (14.3) 1 (50.0) 6 (9.8)
 Not applicable (no NAAT or toxin EIA at the respondent's institution) 0 (0.0) 0 (0.0) 1 (33.3) 1 (33.3) 7 (31.8) 3 (14.3) 0 (0.0) 12 (19.7)
 Unsure 0 (0.0) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 2 (9.5) 0 (0.0) 3 (4.9)
Time interval after the initial CDI episode during which a subsequent episode is classified as a recurrence
 ≤30 days 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (8.0) 4 (14.3) 1 (50.0) 7 (9.9) .92
 ≤56 days 1 (25) 3 (50) 0 (0.0) 0 (0.0) 4 (16.0) 4 (14.3) 1 (50.0) 13 (18.3)
 ≤90 days 1 (25) 0 (0.0) 3 (100.0) 3 (100.0) 9 (36.0) 13 (46.4) 0 (0.0) 29 (40.8)
 ≤120 days 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (12.0) 0 (0.0) 0 (0.0) 3 (4.2)
 ≤180 days 1 (25) 1 (16.7) 0 (0.0) 0 (0.0) 4 (16.0) 2 (7.1) 0 (0.0) 8 (11.3)
 Other 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 1 (4.0) 1 (3.6) 0 (0.0) 3 (4.2)
 Unsure 1 (25) 1 (16.7) 0 (0.0) 0 (0.0) 2 (8.0) 4 (14.3) 0 (0.0) 8 (11.3)
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CCNA = Cell cytotoxicity neutralization assay; CDI = Clostridioides difficile infection; EIA = Enzyme immunoassay; GDH = Glutamate dehydrogenase; NAAT = Nucleic acid amplification test

*

Among the 47 respondents who use two-step testing

†

There were only 61 respondents to this question

Availability and reimbursement of CDI treatments

At their predominant institution of practice and not accounting for reimbursement, 100.0% reported oral vancomycin availability (ie, through formulary or special access request), 89.9% fidaxomicin, and 40.6% fecal microbiota transplantation (FMT) (Table 3). Oral vancomycin was reimbursed (ie, paid for by the institution) by 87.0% of respondents’ institutions. Fidaxomicin reimbursement was reported by 43.5%; of these, 20.0% reported reimbursement for any episode of CDI, whereas the remaining 80.0% reported reimbursement only under certain circumstances (ie, recurrent CDI or particular risk factors).

Table 3:

Availability and funding of CDI therapies

Characteristic Alberta;n = 4 (5.8%) British Columbia;n = 6 (8.7%) Manitoba;n = 3 (4.3%) Atlantic Canada;n = 3 (4.3%) Ontario;n = 24 (34.8%) Quebec;n = 27 (39.1%) Saskatchewan;n = 2 (2.9%) Total;N = 69
Drug availability at institution of practice
 Vancomycin 4 (100.0) 6 (100.0) 3 (100.0) 3 (100.0) 24 (100.0) 27 (100) 2 (100.0) 69 (100.0)
 Fidaxomicin 4 (100.0) 2 (33.3) 3 (100.0) 3 (100.0) 24 (100.0) 24 (88.9) 2 (100.0) 62 (89.9)
 FMT 3 (75) 5 (83.3) 0 (0.0) 3 (100.0) 8 (33.3) 9 (33.3) 0 (0.0) 28 (40.6)
Vancomycin funding indications
 Any episode 4 (100.0) 5 (83.3) 3 (100.0) 3 (100.0) 14 (58.3) 26 (96.3) 2 (100.0) 57 (82.6)
 Certain index episodes 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 2 (8.3) 0 (0.0) 0 (0.0) 3 (4.3)
 Not funded 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (12.5) 0 (0.0) 0 (0.0) 3 (4.3)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (20.8) 1 (3.7) 0 (0.0) 6 (8.7)
Fidaxomicin funding indications*
 Any episode 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.2) 5 (18.5) 0 (0.0) 6 (8.7)
 Certain first episodes 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.2) 8 (29.6) 0 (0.0) 9 (13)
 Any first recurrences 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (8.3) 0 (0.0) 0 (0.0) 2 (2.9)
 Certain first recurrences 1 (25.0) 0 (0.0) 1 (33.3) 1 (33.3) 1 (4.2) 0 (0.0) 0 (0.0) 4 (5.8)
 Any second recurrences 1 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (8.3) 0 (0.0) 1 (50.0) 4 (5.8)
 Certain second recurrences 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 1 (4.2) 2 (7.4) 0 (0.0) 4 (5.8)
 Certain third recurrences 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (50.0) 1 (1.4)
 Not funded 2 (50) 5 (83.3) 2 (66.7) 2 (66.7) 9 (37.5) 8 (29.6) 0 (0.0) 28 (40.6)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 7 (29.2) 4 (14.8) 0 (0.0) 11 (15.9)
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CDI = Clostridioides difficile infection

*

Denotes the earliest indication for which fidaxomicin is funded

Treatment of uncomplicated CDI

For first episodes of CDI, vancomycin was the most common first-line treatment choice for uncomplicated CDI, either with or without respondent-defined risk factors for recurrence (85.3% and 92.6%, respectively; Table 4). For the purposes of selecting a treatment regimen, 40.8% defined a recurrence as occurring within 90 days of a preceding episode of CDI, 18.3% within 56 to 60 days, 11.3% within 180 days, and the remainder selected other time frames or were unsure (Table 2). For first recurrences, the most commonly selected first-line agent was a 4- to 6-week vancomycin pulse and taper (P-T, 61.8%), vancomycin for 10 to 14 days (23.5%), and fidaxomicin (11.8%). A vancomycin P-T (32.4%), 10 days of fidaxomicin (26.5%), a fidaxomicin P-T (13.2%), and FMT (10.3%) were the preferred treatments for second recurrences. For third recurrences, most respondents preferred FMT (32.4%), followed by a vancomycin P-T (13.2%), 10 days of fidaxomicin (13.2%), and a fidaxomicin P-T (10.3%). Across these indications, there were no significant interprovincial differences in treatment selection. The sequential preferred first-line treatments for each indication are depicted in Figure 2, which illustrates the substantial degree of practice variability in later episodes. If systemic antibiotics were required during CDI treatment, most respondents would prolong the CDI treatment to match the duration of systemic antibiotics plus 1 week (64.9%).

Table 4:

Treatment of uncomplicated CDI

Characteristic Alberta;n = 4 (5.9%) British Columbia;n = 6 (8.8%) Manitoba;n = 2 (2.9%) Atlantic Canada;n = 3 (4.4%) Ontario;n = 23 (33.8%) Quebec;n = 28 (41.2%) Saskatchewan;n = 2 (2.9%) Total;N = 68 P value
Uncomplicated CDI without risk factors for recurrence
 Vancomycin 4 (100.0) 6 (100.0) 2 (100.0) 3 (100.0) 21 (91.3) 25 (89.3) 2 (100.0) 63 (92.6) 1.00
 Fidaxomicin 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 2 (7.1) 0 (0.0) 3 (4.4)
 Metronidazole 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 1 (3.6) 0 (0.0) 2 (2.9)
Uncomplicated CDI with risk factors for recurrence
 Vancomycin 4 (100.0) 6 (100.0) 2 (100.0) 3 (100.0) 19 (82.6) 22 (78.6) 2 (100) 58 (85.3) .89
 Fidaxomicin 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (13) 6 (21.4) 0 (0.0) 9 (13.2)
 Other 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 0 (0.0) 0 (0.0) 1 (1.5)
Uncomplicated first recurrence
 Vancomycin 1 (25.0) 1 (16.7) 1 (50.0) 2 (66.7) 6 (26.1) 4 (14.3) 1 (50) 16 (23.5) .80
 Vancomycin P-T 3 (75.0) 5 (83.3) 1 (50.0) 1 (33.3) 14 (60.9) 17 (60.7) 1 (50) 42 (61.8)
 Fidaxomicin 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (8.7) 6 (21.4) 0 (0.0) 8 (11.8)
 Other 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 0 (0.0) 0 (0.0) 1 (1.5)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.6) 0 (0.0) 1 (1.5)
Uncomplicated second recurrence
 Vancomycin P-T 1 (25.0) 1 (16.7) 1 (50.0) 2 (66.7) 8 (34.8) 8 (28.6) 1 (50) 22 (32.4) .77
 Vancomycin P-T + adjunctive agent* 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 2 (8.7) 1 (3.6) 0 (0.0) 4 (5.9)
 Fidaxomicin 2 (50.0) 1 (16.7) 0 (0.0) 0 (0.0) 6 (26.1) 8 (28.6) 1 (50) 18 (26.5)
 Fidaxomicin P-T 0 (0.0) 0 (0.0) 1 (50.0) 0 (0.0) 3 (13) 5 (17.9) 0 (0.0) 9 (13.2)
 Fidaxomicin P-T + adjunctive agent* 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 1 (3.6) 0 (0.0) 2 (2.9)
 FMT 1 (25.0) 3 (50.0) 0 (0.0) 1 (33.3) 1 (4.3) 1 (3.6) 0 (0.0) 7 (10.3)
 Other 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 0 (0.0) 0 (0.0) 1 (1.5)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 4 (14.3) 0 (0.0) 5 (7.4)
Uncomplicated third recurrence
 Vancomycin P-T 0 (0.0) 0 (0.0) 0 (0.0) 1 (33.3) 4 (17.4) 4 (14.3) 0 (0.0) 9 (13.2) .59
 Vancomycin P-T + adjunctive agent* 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (50) 1 (1.5)
 Fidaxomicin 0 (0.0) 0 (0.0) 1 (50.0) 1 (33.3) 5 (21.7) 2 (7.1) 0 (0.0) 9 (13.2)
 Fidaxomicin P-T 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (8.7) 5 (17.9) 0 (0.0) 7 (10.3)
 Fidaxomicin + adjunctive agent* 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.6) 0 (0.0) 1 (1.5)
 Fidaxomicin P-T + adjunctive agent* 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (7.1) 0 (0.0) 2 (2.9)
 FMT 3 (75.0) 3 (50.0) 1 (50.0) 1 (33.3) 8 (34.8) 5 (17.9) 1 (50) 22 (32.4)
 Other 1 (25.0) 1 (16.7) 0 (0.0) 0 (0.0) 1 (4.3) 2 (7.1) 0 (0.0) 5 (7.4)
 Unsure 0 (0.0) 2 (33.3) 0 (0.0) 0 (0.0) 3 (13) 7 (25) 0 (0.0) 12 (17.6)
Respondents would enroll their patients in the following RCTs for first and subsequent CDI recurrences
 Vancomycin P-T versus fidaxomicin 4 (100.0) 4 (66.7) 2 (100.0) 3 (100.0) 21 (91.3) 22 (78.6) 1 (50.0) 57 (83.8) NT
 Vancomycin P-T versus fidaxomicin P-T 3 (75.0) 2 (33.3) 2 (100.0) 3 (100.0) 15 (65.2) 18 (64.3) 1 (50.0) 44 (64.7) NT
 Fidaxomicin versus fidaxomicin P-T 3 (75.0) 0 (0.0) 1 (50.0) 2 (66.7) 14 (60.9) 18 (64.3) 1 (50.0) 39 (57.4) NT
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CDI = Clostridioides difficile infection; FMT = Fecal microbiota transplant; P-T = Pulse and taper

*

Adjunctive agents include commercial microbiota products (VOWST, REBYOTA), bezlotoxumab, or others as defined by the respondent

Figure 2: Alluvial diagram illustrating respondents’ sequential treatment choices for Clostridioides difficile infections, showing how initial treatments relate to those chosen for subsequent recurrences, as indicated by the coloured flows.

Figure 2:

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Practice alignment with the AMMI Canada CDI treatment guideline recommendations (Supplemental Table 1) for 10 to 14 days of oral vancomycin for first episodes of CDI was 85.3%, 14 days of oral vancomycin for first recurrences was 23.5%, a vancomycin P-T for second recurrences was 38.2%, and FMT for third recurrences was 32.4%. For comparison, alignment with the American College of Gastroenterology, Infectious Disease Society of America (IDSA), and European Society of Clinical Microbiology and Infectious Diseases guidelines was also reported in Table 5. Most respondents were willing to enroll their patients in a randomized controlled trial (RCT) comparing a vancomycin P-T to either 10 days of fidaxomicin (83.8%) or fidaxomicin P-T (64.7%), or to 10 days of fidaxomicin versus a fidaxomicin P-T (57.4%) (Table 4).

Table 5:

Adherence to treatment guideline recommendations

Practice AMMI Canada IDSA ACG ESCMID Not adherent to any guidelines
Treatment of uncomplicated CDI
 First episode* Vancomycinn = 58 (85.3%) Fidaxomicinn = 9 (13.2%) Vancomycin or fidaxomicinn = 67 (98.5%) Fidaxomicinn = 9 (13.2%) n = 1 (1.5%)
 First recurrence Vancomycinn = 16 (23.5%) Fidaxomicin P-T ± bezlotoxumabn = 0 (0.0%) Vancomycin P-T if fidaxomicin, metronidazole, or vancomycin was used for the first episode or if vancomycin or metronidazole was used, then fidaxomicinn = 45 (66.2%) If vancomycin or metronidazole was used for the first episode, then fidaxomicin, or if fidaxomicin was used, then addition of bezlotoxumabn = 3 (4.4%) n = 7 (10.3%)
 Second recurrence Vancomycin P-Tn = 26 (38.2%) Fidaxomicin, fidaxomicin P-T, vancomycin P-T, or FMTn = 62 (91.2%) FMTn = 7 (10.3%) FMT or adjunctive bezlotoxumabn = 7 (10.3%) n = 1 (1.5%)
 Third recurrence FMTn = 22 (32.4%) Fidaxomicin, fidaxomicin P-T, vancomycin P-T, or FMTn = 57 (80.8%) FMTn = 22 (32.4%) FMT or adjunctive bezlotoxumabn = 22 (32.4%) n = 1 (1.5%)
Treatment of fulminant CDI
 Without ileus Vancomycin 125–500 mg PO QID + adjunctive IV metronidazolen = 57 (83.8%) Vancomycin 500 mg PO QID + adjunctive IV metronidazolen = 41 (60.3%) Vancomycin 500 mg PO QID + adjunctive IV metronidazolen = 41 (60.3%) Vancomycin 125 mg PO QID or fidaxomicin 200 mg PO BID + consideration of adjunctive tigecyclinen = 5 (7.4%) n = 6 (8.8%)
 With ileus Vancomycin 125–500 mg PO QID + adjunctive IV metronidazole + intrarectal vancomycinn = 51 (75.0%) Vancomycin 500 mg PO QID + adjunctive IV metronidazole + intrarectal vancomycinn = 41 (60.3%) Vancomycin 500 mg PO QID + adjunctive IV metronidazole + intrarectal vancomycinn = 41 (60.3%) Vancomycin 125 mg PO QID or fidaxomicin 200 mg PO BID + consideration of adjunctive tigecyclinen = 0 (0.0%) n = 15 (22.1%)
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ACG = American College of Gastroenterology; BID = Twice a day; CDI = Clostridioides difficile infection; ESCMID = European Society of Clinical Microbiology and Infectious Diseases; FMT = Fecal microbiota transplant; IDSA = Infectious Disease Society of America; IV = Intravenous; PO = Oral; P-T = Pulse and taper; QID = Four times a day

*

Data from first episodes with risk factors for recurrence were used

Treatment of fulminant CDI

For the treatment of fulminant cases of CDI without concomitant ileus, 100% of respondents used oral vancomycin (Table 6). Vancomycin was most commonly dosed at 500 mg four times daily (63.2%); a minority used 125 mg (19.1%) or 250 mg (14.7%) four times a day. In the absence of ileus, 83.8% of respondents added adjunctive intravenous metronidazole, and 17.6% prescribed intrarectal vancomycin in this scenario. For fulminant CDI with ileus, responses were similar (Table 6), but intrarectal vancomycin use was higher (77.9%). There were no significant differences between provinces/regions in the management of fulminant CDI. These responses are 83.8% and 75.0% aligned with the AMMI Canada guidelines for fulminant CDI. Many respondents would consider enrolling their patients with fulminant CDI, regardless of ileus, into the following RCTs: vancomycin 125 mg versus 500 mg four times daily (54.4%), vancomycin (250–500 mg) versus fidaxomicin (73.5%), and adjunctive intravenous metronidazole versus tigecycline (52.9%).

Table 6:

Treatment of fulminant CDI

Characteristic Alberta;n = 4 (5.9%) British Columbia;n = 6 (8.8%) Manitoba;n = 2 (2.9%) Atlantic Canada;n = 3 (4.4%) Ontario;n = 23 (33.8%) Quebec;n = 28 (41.2%) Saskatchewan;n = 2 (2.9%) Total;N = 68 P value
Fulminant CDI without ileus
 Oral CDI antibiotic
  Vancomycin 4 (100.0) 6 (100.0) 2 (100.0) 3 (100.0) 23 (100.0) 28 (100.0) 2 (100.0) 68 (100.0) 1.00
 Dose of oral vancomycin
  125 mg four times daily 2 (50.0) 2 (33.3) 0 (0.0) 0 (0.0) 3 (13) 5 (17.9) 1 (50.0) 13 (19.1) .96
  250 mg four times daily 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 5 (21.7) 4 (14.3) 0 (0.0) 10 (14.7)
  500 mg four times daily 2 (50.0) 2 (33.3) 2 (100.0) 3 (100.0) 14 (60.9) 19 (67.9) 1 (50.0) 43 (63.2)
  Other 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 0 (0.0) 0 (0.0) 1 (1.5)
  Unsure 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.5)
 Adjunctive treatment
  Intravenous metronidazole 4 (100.0) 3 (50.0) 2 (100.0) 2 (66.7) 19 (82.6) 25 (89.3) 2 (100.0) 57 (83.8) .92
  No adjunctive agent 0 (0.0) 3 (50.0) 0 (0.0) 1 (33.3) 4 (17.4) 3 (10.7) 0 (0.0) 11 (16.2)
 Intrarectal vancomycin
  Yes 1 (25.0) 2 (33.3) 1 (50.0) 1 (33.3) 1 (4.3) 4 (14.3) 2 (100.0) 12 (17.6) .33
  No 3 (75.0) 4 (66.7) 1 (50.0) 2 (66.7) 22 (95.7) 24 (85.7) 0 (0.0) 56 (82.4)
Fulminant CDI with ileus
 Oral CDI antibiotic
  Vancomycin 4 (100.0) 5 (83.3) 2 (100.0) 3 (100.0) 23 (100.0) 27 (96.4) 2 (100.0) 66 (97.1) .97
  Unsure 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.6) 0 (0.0) 2 (2.9)
 Dose of oral vancomycin
  125 mg four times daily 2 (50.0) 1 (16.7) 0 (0.0) 0 (0.0) 2 (8.7) 2 (7.1) 1 (50.0) 8 (11.8) .87
  250 mg four times daily 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 5 (21.7) 4 (14.3) 0 (0.0) 10 (14.7)
  500 mg four times daily 2 (50.0) 3 (50.0) 2 (100.0) 3 (100.0) 15 (65.2) 22 (78.6) 1 (50.0) 48 (70.6)
  Other 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.3) 0 (0.0) 0 (0.0) 1 (1.5)
  Unsure 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.5)
 Adjunctive treatment
  Intravenous metronidazole 4 (100.0) 5 (83.3) 2 (100.0) 3 (100.0) 21 (91.3) 26 (92.9) 2 (100.0) 63 (92.6) .98
  Intravenous tigecycline 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.6) 0 (0.0) 1 (1.5)
  No adjunctive agent 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (8.7) 0 (0.0) 0 (0.0) 2 (2.9)
  Unsure 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.6) 0 (0.0) 2 (2.9)
 Intrarectal vancomycin
  Yes 3 (75.0) 2 (33.3) 2 (100.0) 3 (100.0) 18 (78.3) 23 (82.1) 2 (100.0) 53 (77.9) .92
  No 1 (25.0) 3 (50.0) 0 (0.0) 0 (0.0) 5 (21.7) 4 (14.3) 0 (0.0) 13 (19.1)
  Unsure 0 (0.0) 1 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.6) 0 (0.0) 2 (2.9)
Respondents would enrol their patients in the following RCTs for fulminant CDI regardless of ileus
 Vancomycin 500 mg versus 125 mg PO QID 3 (75.0) 4 (66.7) 1 (50.0) 3 (100.0) 13 (56.5) 12 (42.9) 1 (50.0) 37 (54.4) NT
 Vancomycin 250–500 mg PO QID versus fidaxomicin 4 (100.0) 2 (33.3) 2 (100.0) 3 (100.0) 19 (82.6) 19 (67.9) 1 (50.0) 50 (73.5) NT
 Adjunctive intravenous metronidazole versus tigecycline 4 (100.0) 3 (50.0) 2 (100.0) 1 (33.3) 12 (52.2) 13 (46.4) 1 (50.0) 36 (52.9) NT
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CDI = Clostridioides difficile infection; PO = Oral; NT = Not tested; QID = Four times a day

CDI prophylaxis

The AMMI Canada guidelines (5) state that secondary prophylaxis with oral vancomycin during antibiotic re-exposure may be considered in patients with a recent history of fulminant or multiple recurrent CDI. Most respondents had used secondary CDI prophylaxis during antibiotic re-exposure (83.9%), but there was heterogeneity between provinces/regions (P < .001, Table 7). For example, use of secondary prophylaxis was reported by 97.9% and 100.0% of respondents from Quebec and Alberta, compared to 79.4% in Ontario and 50.0% in British Columbia and Saskatchewan. Among users of secondary prophylaxis, 58.5% of respondents used prophylaxis only after one episode of CDI, 34.0% after a first recurrence, and 2.1% after two recurrences, with significant interprovincial differences (P = .03). Secondary prophylaxis was considered only within 3 months of the index episode of CDI by 21.3%, within 6 months by 29.8%, and within 1 year by 37.2%. Vancomycin was the most frequently used prophylactic agent (97.9%). The most common dose was 125 mg twice daily (55.4%), followed by 125 mg once daily (33.7%) or four times daily (8.7%). Respondents most often gave secondary CDI prophylaxis for the duration of systemic antibiotics plus 1 week (71.3%) or only for the duration of systemic antibiotics (16.0%), with significant interprovincial differences (P = .004). Irrespective of prophylaxis use, 91.1% of participants would randomize their patients to an RCT of secondary vancomycin prophylaxis versus placebo during antibiotic re-exposure.

Table 7:

Secondary CDI prophylaxis

Characteristic Alberta;n = 8 (7.1%) British Columbia;n = 14 (12.5%) Manitoba;n = 4 (3.6%) Atlantic Canada;n = 3 (2.7%) Ontario;n = 34 (30.4%) Quebec;n = 47 (42.0%) Saskatchewan;n = 2 (1.8%) Total;N = 112 P value
Use of secondary CDI prophylaxis
 Yes 8 (100.0) 7 (50.0) 3 (75.0) 2 (66.7) 27 (79.4) 46 (97.9) 1 (50.0) 94 (83.9) <.001*
 No 0 (0.0) 7 (50.0) 1 (25.0) 1 (33.3) 7 (20.6) 1 (2.1) 1 (50.0) 18 (16.1)
After how many prior episodes of CDI is secondary C. difficile prophylaxis used
 ≤1 3 (37.5) 2 (28.6) 1 (33.3) 0 (0.0) 14 (51.9) 35 (76.1) 0 (0.0) 55 (58.5) .034*
 ≤2 5 (62.5) 4 (57.1) 2 (66.7) 2 (100.0) 9 (33.3) 9 (19.6) 1 (100.0) 32 (34)
 ≤3 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.7) 1 (2.2) 0 (0.0) 2 (2.1)
 Unsure 0 (0.0) 1 (14.3) 0 (0.0) 0 (0.0) 3 (11.1) 1 (2.2) 0 (0.0) 5 (5.3)
Time frame after CDI during which C. difficile prophylaxis is considered
 Any time 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (11.1) 1 (2.2) 0 (0.0) 4 (4.3) .54
 <5 years 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (7.4) 1 (2.2) 0 (0.0) 3 (3.2)
 <1 year 3 (37.5) 2 (28.6) 2 (66.7) 0 (0.0) 8 (29.6) 20 (43.5) 0 (0.0) 35 (37.2)
 <6 months 4 (50) 4 (57.1) 1 (33.3) 0 (0.0) 6 (22.2) 13 (28.3) 0 (0.0) 28 (29.8)
 <3 months 1 (12.5) 0 (0.0) 0 (0.0) 2 (100.0) 7 (25.9) 9 (19.6) 1 (100.0) 20 (21.3)
 Unsure 0 (0.0) 1 (14.3) 0 (0.0) 0 (0.0) 1 (3.7) 2 (4.3) 0 (0.0) 4 (4.3)
Agent used for C. difficile prophylaxis
 Vancomycin 8 (100) 7 (100.0) 3 (100.0) 2 (100.0) 26 (96.3) 45 (97.8) 1 (100) 92 (97.9) .76
 Metronidazole 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.7) 0 (0.0) 0 (0.0) 1 (1.1)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.2) 0 (0.0) 1 (1.1)
Dose of vancomycin prophylaxis
 125 mg once daily 2 (25.0) 3 (42.9) 1 (33.3) 1 (50.0) 11 (42.3) 13 (28.9) 0 (0.0) 31 (33.7) .77
 125 mg twice daily 5 (62.5) 4 (57.1) 2 (66.7) 1 (50.0) 13 (50) 26 (57.8) 0 (0.0) 51 (55.4)
 125 mg four times daily 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.8) 5 (11.1) 1 (100.0) 8 (8.7)
 A taper 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.2) 0 (0.0) 1 (1.1)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) 0 (0.0) 1 (1.1)
Approximate frequency of CDI prophylaxis use
 0% 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (7.4) 1 (2.2) 0 (0.0) 3 (3.2) .068
 25% 3 (37.5) 3 (42.9) 1 (33.3) 2 (100.0) 9 (33.3) 9 (19.6) 1 (100.0) 28 (29.8)
 50% 3 (37.5) 0 (0.0) 2 (66.7) 0 (0.0) 6 (22.2) 5 (10.9) 0 (0.0) 16 (17)
 75% 2 (25) 2 (28.6) 0 (0.0) 0 (0.0) 7 (25.9) 12 (26.1) 0 (0.0) 23 (24.5)
 100% 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (7.4) 16 (34.8) 0 (0.0) 18 (19.1)
 Unsure 0 (0.0) 2 (28.6) 0 (0.0) 0 (0.0) 1 (3.7) 3 (6.5) 0 (0.0) 6 (6.4)
Duration of prophylaxis
 8–14 days fixed duration 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.7) 0 (0.0) 0 (0.0) 1 (1.1) .0038*
 For the duration of systemic antibiotics 3 (37.5) 1 (14.3) 0 (0.0) 1 (50.0) 6 (22.2) 4 (8.7) 0 (0.0) 15 (16)
 For the duration of systemic antibiotics + 1 week 4 (50.0) 5 (71.4) 3 (100.0) 1 (50.0) 13 (48.1) 41 (89.1) 0 (0.0) 67 (71.3)
 Other 1 (12.5) 1 (14.3) 0 (0.0) 0 (0.0) 7 (25.9) 1 (2.2) 1 (100.0) 11 (11.7)
Treatment prolongation when systemic antibiotics are required during CDI treatment
 Not prolonged 1 (12.5) 0 (0.0) 0 (0.0) 1 (50.0) 2 (7.4) 3 (6.5) 0 (0.0) 7 (7.4) <.001*
 1–7 days fixed 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.7) 1 (2.2) 0 (0.0) 3 (3.2)
 8–14 days fixed 0 (0.0) 1 (14.3) 1 (33.3) 0 (0.0) 0 (0.0) 1 (2.2) 1 (100.0) 4 (4.3)
 Duration of systemic antibiotics 2 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (18.5) 1 (2.2) 0 (0.0) 8 (8.5)
 Duration of systemic antibiotics + 1 week 2 (25.0) 4 (57.1) 2 (66.7) 1 (50.0) 13 (48.1) 39 (84.8) 0 (0.0) 61 (64.9)
 Other 2 (25.0) 2 (28.6) 0 (0.0) 0 (0.0) 4 (14.8) 1 (2.2) 0 (0.0) 9 (9.6)
 Unsure 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (7.4) 0 (0.0) 0 (0.0) 2 (2.1)
Would randomize patients to vancomycin prophylaxis versus placebo
 Yes 7 (87.5) 12 (85.7) 4 (100.0) 3 (100.0) 32 (94.1) 42 (89.4) 2 (100.0) 102 (91.1) NT
 No 1 (12.5) 2 (14.3) 0 (0.0) 0 (0.0) 2 (5.9) 5 (10.6) 0 (0.0) 10 (8.9)
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CDI = Clostridioides difficile infection; NT = Not tested

Note: Percentages are computed according to the number of respondents relevant for that category

*

Statistically significant values <.05

Discussion

This study provides a comprehensive overview of real-world Canadian CDI practices. While our international survey highlighted global variability in CDI practice (13), the present study demonstrates that many of these heterogeneous practices persist within Canada despite the availability of a national guideline (5).

For the treatment of recurrent CDI, practice was less commonly aligned (<40%) with the Canadian guidelines (5). Similarly, low guideline uptake was recorded in the United States when the 2021 IDSA guidelines were released (17). Since the publication of the Canadian guidelines in 2018 that recommended vancomycin as first-line treatment for first recurrence (5), other international guidelines have put a greater emphasis on fidaxomicin (10–12), which may have contributed to increased use in Canada. Practice variability (use of vancomycin versus fidaxomicin) may reflect a more cost-conscious interpretation of the literature, coupled with differences in provincial or institutional drug coverage affecting the availability and reimbursement of fidaxomicin (9). FMT use for third recurrences was low (30%), potentially due to low availability (around 40% respondents) (18).

There was significant heterogeneity identified across Canada in the use, duration, timing, and dosing of secondary CDI prophylaxis during antibiotic re-exposure. Overall, use of prophylaxis was particularly high in Canada compared to other countries (13). While Canadian guidelines suggest consideration of prophylaxis for patients with a history of multiply recurrent or fulminant CDI (5), data supporting this practice are poor quality (19), and international guideline recommendations for prophylaxis are conflicting (10–12). Higher-quality data are needed.

Inherent to its survey design, there exists certain limitations to this study. First, response rates were low from some less populated provinces/territories. Second, nonresponse bias could not be quantified. Third, there may have been selection bias, which we attempted to mitigate using a multifaceted recruitment strategy. Fourth, response bias from social desirability and undue influence of memorable cases may have led to inaccurate and unrepresentative responses. Nevertheless, this is the first and largest study describing the practice patterns of CDI in Canada.

Conclusion

This survey of Canadian clinicians’ CDI practices identified that clinician practice often does not align with national guidelines for the treatment of recurrent CDI and noted a lack of consensus across multiple areas of CDI management and prevention. High-quality RCTs were highly supported by the respondents, ideally as a platform trial, which should help reconcile heterogeneous practice to generate a more evidence-based Canadian standard of CDI care.

Acknowledgements

The authors thank the respondents who volunteered their time to participate.

Funding Statement

No funding was received for this work.

Contributors

Conceptualization, C Prosty, T Lee, EG McDonald; Methodology, C Prosty, T Lee, EG McDonald; Software, C Prosty; Validation, B Desormeau, T Lee, EG McDonald; Formal Analysis, C Prosty; Investigation, C Prosty, EG McDonald; Resources, C Prosty; Data Curation, C Prosty; Writing – Original Draft, C Prosty, T Lee, EG McDonald; Writing – Review & Editing, C Prosty, B Desormeau, T Lee, EG McDonald; Visualization, C Prosty; Supervision, EG McDonald; Project Administration, C Prosty, T Lee, EG McDonald; Funding Acquisition, EG McDonald.

Ethics Approval

This study was approved by the McGill University Health Centre Research Ethics Board (2025-10917).

Informed Consent

Informed consent was implied by response to the survey.

Registry and the Registration No. of the Study/Trial

N/A

Data Accessibility

All data will not be made publicly available. Researchers who require access to the study data can contact the corresponding author for further information.

Funding

No funding was received for this work.

Disclosures

Drs Prosty, Lee, and McDonald are co-applicants on a Canadian Institutes of Health Research operating grant proposal to fund a CDI platform randomized clinical trial.

Peer Review

This article has been peer reviewed.

Animal Studies

N/A

Supplemental Material

References

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

jammi-11-1-2025-0014_supplement1.pdf (113.9KB, pdf)

Data Availability Statement

All data will not be made publicly available. Researchers who require access to the study data can contact the corresponding author for further information.

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