Table 3. Main characteristics of the studies included in the review.

CD: Crohn’s disease, CDI: C. difficile infection, FMT: fecal microbiota transplantation, IBD: inflammatory bowel disease, NSAID: non-steroidal anti-inflammatory drug, UC: ulcerative colitis

Author	Year	Location	Title	Type of study	Identified risk factors	Management outcomes
Boeriu et al. [11]	2022	Romania	The current knowledge on Clostridioides difficile infection in patients with inflammatory bowel disease	Literature review	Increasing age and comorbidities, gut microbiota disturbance, antibiotics use, nonsteroidal anti-inflammatory drugs within two months prior to hospital risk, pancolitis, corticosteroids, and biologic therapies, interleukin-4 single nucleotide polymorphisms	Oral vancomycin 125 mg four times a day for 10 days is the first-line treatment, it also reduces the necessity for colectomy. Due to rates of recurrence after vancomycin, fidaxomicin 200 mg daily for 10 days is used as an alternative for initial treatment. With an increase of hypervirulent strains resistant to traditional management, monoclonal antibodies actoxumab and bezlotoxumab are now used
Del Vecchio et al. [12]	2022	Italy	Risk factors, diagnosis, and management of Clostridioides difficile infection in patients with inflammatory bowel disease	Literature review	Antibiotic use, colonic involvement, dysbiotic gut microbiota, NSAID, corticosteroid, and biological therapies	Use of vancomycin and fidaxomicin are the first-line treatment therapies, if they are not available metronidazole is administered. The first recurrence of CDI should be treated with different antibiotic regimens from the first episode. A safer and more tolerable option for recurrent CDI is FMT
Khanna et al. [13]	2021	USA	Management of Clostridioides difficile infection in patients with inflammatory bowel disease	Literature review	Antibiotic use, dysbiosis in gut microbiota	Vancomycin and fidaxomicin are recommended as first-line treatment, metronidazole is no longer recommended for the management of CDI. Prevention for recurrence is avoiding risk factors and optimal management of IBD with a goal of remission. Fidaxomicin is used for the first recurrence and to prevent future recurrent CDI FMT is used
Sehgal et al. [14]	2021	USA	The interplay of Clostridioides difficile infection and inflammatory bowel disease	Literature review	Dysbiosis in gut microbiota, antibiotic use, immunosuppressive therapy, prior CDI, hospitalization, surgeries, stay in a long-term care facility	In broad terms, there are three treatment options for CDI in IBD patients: pharmacotherapy, FMT, and surgery. The initial episode of CDI is treated with vancomycin or fidaxomicin for 10 days, and metronidazole is not recommended. For the first recurrence, fidaxomicin is used, but its cost is an ongoing challenge. FMT is emerging as the preferred option for recurrent CDI in patients with underlying IBD. The decision of titration of immunosuppression therapy for IBD patients with superimposed CDI is made on an individual basis
Tariq et al. [15]	2021	USA	Outcomes of fecal microbiota transplantation for C. difficile infection in inflammatory bowel disease: a systematic review and meta-analysis	Systematic review and meta-analysis	Disruption of healthy gut microbiota	FMT is a safe and effective therapy for CDI, with an overall cure rate higher in multiple FMTs than in a single FMT. Twenty-five percent of patients experienced IBD flare after FMT. Less than 10% of adults underwent colectomy after FMT, most of them due to worsening IBD
Yue et al. [16]	2020	China	Regulation of the intestinal microbiota: an emerging therapeutic strategy for inflammatory bowel disease	Literature review	Dysbiosis in gut microbiota	Treatments targeting intestinal microbiota, probiotics, prebiotics, symbiotics, herbal medicine, and FMT implement therapeutic action by correcting dysbiosis. With current treatment methods offering low effectiveness with the rapid rise in IBD incidence, these complementary and alternative therapies should be considered
Balram et al. [17]	2019	USA	Risk factor associated with Clostridium difficile infection in inflammatory bowel disease: a systematic review and meta-analysis	Systematic review and meta-analysis	Antibiotic use, colonic involvement, biologic medication	IBD patients with CDI have an almost fourfold increase in risk of in-hospital and long-term mortality, justifying the need for rapid diagnosis and aggressive treatment. CDI doubled the odds of having colectomy in the long term. It is not associated with a short-term risk of colectomy
Beniwal-Patel et al. [18]	2019	USA	The juncture between Clostridioides difficile infection and inflammatory bowel diseases	Literature review	Antibiotic use, restorative procto-colectomy with ileal pouch-anal anastomosis, NSAID within two months prior to admission, history of CD within the past 12 months, emergency department visits 12 weeks prior to admission	For first-time CDI, initial therapy consists of either vancomycin or fidaxomicin. The option to stop immunosuppression therapy has not been well studied, but it is important to consider that biological therapies have very long half-lives, so a cease in therapy would not stop the immunosuppression
Moens et al. [19]	2019	Belgium	Clostridium difficile infection in inflammatory bowel disease: epidemiology over two decades	Case and control	Dysbiosis in gut microbiota, colonic involvement, corticosteroids	Vancomycin is recommended as first-line treatment, lower rates of recurrent CDI after vancomycin could not be confirmed in the cohort used. The number of FMT for recurrent CDI was very low due to cases of refractory CDI being excluded as they were not established in the hospital. The association between the risk of colectomy and CDI has yielded inconsistent results with a lot of heterogeneity in the studies observed
Chen et al. [20]	2018	China	Effect of faecal microbiota transplantation for treatment of Clostridium difficile infection in patients with inflammatory bowel disease: a systematic review and meta-analysis of cohort studies	Systematic review and meta-analysis	Hospital stays, recurrence despite receiving standard treatment	Usual treatment includes metronidazole or vancomycin results in recurrence rates between 22-34%. The use of FMT normalizes gut dysbiosis, with an initial cure rate of 81% [95% CI= 76-85%], demonstrating it as an effective therapy for CDI in patients with IBD
Chen et al. [21]	2017	Australia	Clostridium difficile infection and risk of colectomy in patients with inflammatory bowel disease: a bias-adjusted meta-analysis	Meta-analysis	Dysbiotic gut microbiota, severe IBD flares, elevated surgical rates, colonic involvement, immunomodulatory therapy	Initial management for IBD is medical therapy until there is a failure in treatment or complications occur, which then should be followed by colectomy. UC has higher surgical rates due to it being limited to the colon, compared to CD
D’Aoust et al. [22]	2017	Canada	Management of inflammatory bowel disease with Clostridium difficile infection	Systematic review	Broad-spectrum antibiotic exposure, recent hospitalization, immunosuppression, increased age, comorbidities, interleukin-4-associated single nucleotide polymorphism	For Mild to moderate CDI, the use of metronidazole or vancomycin is recommended, when the disease is severe or with complications the use of vancomycin is first-line therapy. For the first recurrence of CDI, treatment includes metronidazole, vancomycin, and fidaxomicin. Subsequent recurrence should consider FMT