Clostridium difficile Infection: A Rarity in Patients Receiving Chronic Antibiotic Treatment for Crohn's Disease.

Dysbiosis refers to an alteration in the bacterial composition of the bowel. Dysbiosis is considered to play a significant role in the pathogenesis of numerous conditions affecting human health, including Crohn’s disease (CD). A rapidly increasing body of literature has shown that patients with CD have reduced microbiome diversity and shifts in the concentrations of both protective and invasive bacterial species.1–13 A recent systematic review of 72 abstracts showed that the relative abundance of Bacteroidetes and Enterobacteriaceae (specifically Eschericia coli) are increased in CD, whereas Firmicutes and Faecalibacterium prausnitzii are found at lower abundance.14 Evidence suggests that dysbiosis may play an important role in initiating and maintaining the chronic inflammation that characterizes CD. Given the impact of the microbiome, CD commonly affects areas of the gastrointestinal tract with high bacterial concentrations, such as the terminal ileum and colon. Antibiotic therapy is thought to favorably alter the microbiome in patients with CD and reduce bacterial invasion into gut tissue.15–18 Although studies in animals have shown antibiotics to be effective in acute and chronic colitis and ileitis,19 the role of antibiotics in the treatment of active CD in humans is unclear. Current guidelines only recommend the use of antibiotics in perianal disease, bacterial overgrowth, and infectious complications of CD.20 A recent meta-analysis including 16 randomized control trials in varied CD populations showed that antibiotics may be effective in inducing remission and preventing relapse.21 Therefore, some patients are prescribed chronic antibiotics as a component of their CD treatment. The prolonged use of antibiotics for any medical condition raises the concern for Clostridium difficile infection (CDI). Two studies following patients with left ventricular assist device infections and infected orthopedic prostheses who required varied antibiotic regimens for an average duration of 15.2 and 48.9 months, respectively. The rates of CDI in these 2 studies were reported at 12.5% and 22.2%.22,23 The incidence of CDI is of particular concern in patients with inflammatory bowel disease (IBD). Not only is there an increased incidence of CDI in this population, CDI often induces disease relapse and is associated with higher rates of colectomy.24 In the largest existing cohort study following more than 350,000 patients with IBD over 10 years in the United States, CDI was diagnosed in 2.8% of patients with ulcerative colitis and 1.0% of patients with CD.25 In another study evaluating the incidence of CDI in patients hospitalized between 1998 and 2004, the incidence of CDI in hospitalized patients with ulcerative colitis and CD was 3.73% and 1.09%, respectively, whereas the incidence in the general population was only 0.45%.26 Further studies have shown that the overall incidence of CDI in patients with IBD has increased significantly over the last 2 decades.27–30 Potential risk factors that have been identified for CDI in patients with IBD include IBD subtype, older age, steroid use, severity of disease, extent of disease, and recent antibiotic therapy.27,31,32 Although some retrospective studies have shown that CDI incidence in patients with IBD may be associated with previous antibiotic use,27 to date there has not been any study specifically evaluating the incidence of CDI in patients receiving chronic antibiotic therapy. In this study, we aim to determine the incidence of CDI in patients with CD being treated with chronic antibiotics. The secondary aim of this study was to describe the specific clinical characteristics of patients with CD who develop CDI with chronic antibiotic treatment.