Diagnosis and Management of C. Difficile in Patients With IBD

Fecal Microbiota Transplantation for Recurrent Clostridioides Difficile Infection in Inflammatory Bowel Disease

IBD patients with recurrent CDI should be referred for consideration of FMT, which has been shown to be safe and effective.^[23] As patients with colonic IBD are at higher risk for CDI recurrence, it is hypothesized that colonic dysbiosis due to chronic colitis predisposes these patients to CDI.^[55] This dysbiosis may be restored by FMT, which involves the instillation of microbial communities derived from healthy donor stool into the affected individual's gastrointestinal tract. In a retrospective study of patients receiving FMT after at least two recurrences of CDI, FMT successfully cleared CDI in 74.4% of patients.^[69] However, non-IBD patients in this cohort had a higher rate of CDI clearance at 92.1%. In another cohort study, 75% of patients with IBD had response to FMT for recurrent CDI, which was similar to the response in non-IBD patients.^[70] Tariq and colleagues performed a retrospective study of 145 IBD patients undergoing FMT for recurrent CDI and found that FMT induced a CDI cure rate of 80% with no further recurrence after a median of 9.3 months of follow-up.^[71] Our group recently performed a prospective multicenter cohort study of FMT in 49 IBD patients with recurrent CDI, which demonstrated a 10% rate of FMT failure at week 8.^[72] All initial nonresponders achieved clinical cure after a second FMT and successful C. difficile decolonization was achieved in 45/49 (91.8%) patients.

Prospective data suggest that FMT may also have a beneficial effect on the clinical course of IBD.^[73–75] Moayyedi et al.^[73] performed a placebo-controlled trial of 70 patients with active ulcerative colitis without infectious diarrhea, which found that 24% of those receiving FMT achieved remission at 7 weeks compared with 5% of those receiving placebo. In another RCT of 85 ulcerative colitis patients, Paramsothy et al.^[74] demonstrated that FMT-induced remission in 27% of patients compared with 8% for placebo. FMT was also associated with an increase in microbial diversity in this study. In a systematic review and meta-analysis of four RCTs, FMT was associated with higher rates of endoscopic and clinical remission of ulcerative colitis compared with placebo (number needed to treat = 5) with no difference in adverse events.^[76] In a secondary analysis of our group's prospective cohort study, rates of clinical improvement were 73.3% for ulcerative colitis and 62% for Crohn's disease at 12 weeks after FMT.^[77] Only one of 49 patients experienced a de-novo flare.

Prior studies also suggest that FMT is safe in the IBD population. In a systematic review of 4 RCTs of FMT used for active ulcerative colitis, there was no significant increase in serious adverse events compared with controls.^[76] Our group also identified only two serious adverse events prospectively among 49 IBD patients after FMT for recurrent CDI, and neither of these was felt to be treatment-related.^[72]

Table 1. Studies evaluating the association between immunosuppressive medications and clinical outcomes in the setting of *Clostridioides difficile* infection among patients with inflammatory bowel disease
Reference (journal)	Design and population	Outcomes
Ben-Horin et al.[78] Clinical Gastroenterology and Hepatology	Multicenter retrospective cohort European Crohn's and Colitis Organization 155 Hospitalized IBD patients with CDI (2001–2008)	1. No independent association between immunosuppressive medications and composite outcome (death within 3 months, megacolon, bowel perforation, shock, respiratory failure): LR 11.9, 95% CI 0.9–157 2. Higher adjusted odds of composite outcome associated with 2 or more immunosuppressive medications: OR 17, 95% CI 3.1–91
Ananthakrishnan et al.[79] Alimentary Pharmacology and Therapeutics	Multiinstitutional retrospective cohort Boston, MA, USA 294 hospitalized IBD patients with CDI (1998–2010)	1. No association between immunomodulators and severe outcomes (time to colectomy or death): HR 0.57, 95% CI 0.4–1.2 2. No association between corticosteroids and severe outcomes: HR 0.9, 95% CI −0.5–1.5 3. No association between anti-TNFs and severe outcomes: HR 0.4, 95% CI 0.1–1.5
Solanky et al.[80] Inflammatory Bowel Diseases	Single-center retrospective cohort Rochester, MN, USA 137 hospitalized IBD patients with CDI (2008–2013)	1. Higher adjusted odds of colon surgery within 1 year after CDI associated with corticosteroid use: OR 5.9, 95% CI 2.0–17.4
Lukin et al.[82] Inflammatory Bowel Diseases	Multicenter retrospective cohort New York, NY, USA 207 hospitalized IBD patients with CDI (dates unknown)	1. Lower adjusted odds of severe outcomes (death, sepsis, or colectomy within 90 days) associated with IBD therapy escalation to corticosteroids or biologics: OR 0.12, 95% CI 0.02–0.9
Bar-Yoseph et al.[81] International Journal of Colorectal Disease	Single-center retrospective cohort Haifa, Israel 113 hospitalized IBD patients with CDI (2002–2018)	1. No significant difference in 1-year colectomy rates by exposure to early corticosteroids (within 48 h of admission): 8.5 vs. 0.0%, P = 0.192. 2. No significant difference in 1-year mortality rates by exposure to early corticosteroids: 6.1 vs. 16.1%, P = 0.13

Table 1. Studies evaluating the association between immunosuppressive medications and clinical outcomes in the setting of Clostridioides difficile infection among patients with inflammatory bowel disease

Reference (journal)

Design and population

Outcomes

Ben-Horin et al.[78]
Clinical Gastroenterology and Hepatology

Multicenter retrospective cohort
European Crohn's and Colitis Organization
155 Hospitalized IBD patients with CDI (2001–2008)

1. No independent association between immunosuppressive medications and composite outcome (death within 3 months, megacolon, bowel perforation, shock, respiratory failure): LR 11.9, 95% CI 0.9–157
2. Higher adjusted odds of composite outcome associated with 2 or more immunosuppressive medications: OR 17, 95% CI 3.1–91

Ananthakrishnan et al.[79]
Alimentary Pharmacology and Therapeutics

Multiinstitutional retrospective cohort
Boston, MA, USA
294 hospitalized IBD patients with CDI (1998–2010)

1. No association between immunomodulators and severe outcomes (time to colectomy or death): HR 0.57, 95% CI 0.4–1.2
2. No association between corticosteroids and severe outcomes: HR 0.9, 95% CI −0.5–1.5
3. No association between anti-TNFs and severe outcomes: HR 0.4, 95% CI 0.1–1.5

Solanky et al.[80]
Inflammatory Bowel Diseases

Single-center retrospective cohort
Rochester, MN, USA
137 hospitalized IBD patients with CDI (2008–2013)

1. Higher adjusted odds of colon surgery within 1 year after CDI associated with corticosteroid use: OR 5.9, 95% CI 2.0–17.4

Lukin et al.[82]
Inflammatory Bowel Diseases

Multicenter retrospective cohort
New York, NY, USA
207 hospitalized IBD patients with CDI (dates unknown)

1. Lower adjusted odds of severe outcomes (death, sepsis, or colectomy within 90 days) associated with IBD therapy escalation to corticosteroids or biologics: OR 0.12, 95% CI 0.02–0.9

Bar-Yoseph et al.[81]
International Journal of Colorectal Disease

Single-center retrospective cohort
Haifa, Israel
113 hospitalized IBD patients with CDI (2002–2018)

1. No significant difference in 1-year colectomy rates by exposure to early corticosteroids (within 48 h of admission): 8.5 vs. 0.0%, P = 0.192.
2. No significant difference in 1-year mortality rates by exposure to early corticosteroids: 6.1 vs. 16.1%, P = 0.13