Diagnosis and Management of C. Difficile in Patients With IBD

Abstract and Introduction

Abstract

Purpose of Review: Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD.

Recent Findings: Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed.

Summary: CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy.

Introduction

Clostridioides difficile is an anaerobic, spore-forming bacterium and a leading cause of nosocomial diarrhea in the United States.^[1] In 2011, there were an estimated 453 000 cases of initial C. difficile infection (CDI) and 29 300 CDI-associated deaths.^[2] Due to efforts to reduce healthcare-associated infections, the incidence of CDI improved from 154.9 to 143.6 per 100 000 persons between 2011 and 2017.^[3] However, patients with inflammatory bowel disease (IBD) have a nearly five-fold increase in risk of CDI compared with the general population.^[4] In this review, we will summarize the most recent data regarding risk factors of CDI, the clinical presentations and diagnostic criteria for CDI, management of the initial episode as well as recurrent CDI, and management of IBD exacerbation in the setting of CDI.

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