Diagnosis and Management of Clostridioides Difficile Infection in Patients With Inflammatory Bowel Disease

Rahul S. Dalal; Jessica R. Allegretti


Curr Opin Gastroenterol. 2021;37(4):336-343. 

In This Article

Medical Management of Recurrent Clostridioides Difficile Infection

Recurrence of CDI requires the resolution of symptoms followed by recurrence of symptoms and a positive stool test for C. difficile within 8 weeks after discontinuation of appropriate CDI therapy.[1] This can be due to relapse of the original strain or infection with a new strain of C. difficile.[50,51] In the general population, CDI recurs in 10–35% of patients.[52–54] However, patients with IBD are 33% more likely to experience CDI recurrence.[55] Risk factors for recurrent CDI in the IBD population include Crohn's colitis and recent use of antibiotics, 5-aminosalicylic acid medications, corticosteroids, or infliximab relative to index CDI.[55]

All patients with recurrent diarrhea but negative stool testing for C. difficile should be evaluated for other causes, including postinfectious irritable bowel syndrome (IBS). The prevalence of IBS at 12 months after an enteritis due to any infectious organism is estimated at 10%.[56] In a retrospective cohort study of patients treated successfully for CDI, 25% of patients with no prior history of IBS met Rome III criteria for IBS with diarrhea after 6 months.[57] Additional risk factors for post-CDI IBS included history of anxiety and higher BMI. In a recent prospective cohort study, preexisting IBD was independently associated with new gastrointestinal symptoms (bloating, constipation, or loose stools) after successful cure of CDI by FMT.[58]

If a first recurrence of CDI is confirmed by two-step stool testing, subsequent therapy should be distinct from the first regimen. Patients initially treated with a standard regimen of oral vancomycin should receive a pulse-tapered regimen of oral vancomycin which includes 125 mg daily for 14 days followed by twice daily for 7 days, once daily for 7 days, and then once every 2–3 days for 2–8 weeks.[1] Oral fidaxomicin 200 mg twice daily for 10 days is another option for these patient.[59] For those that initially received oral fidaxomicin or metronidazole, a standard 10-day regimen of oral vancomycin is the appropriate next therapy. Data regarding the medication regimens effective for second or further recurrence of CDI are limited, and no distinct recommendations exist for patients with IBD. An oral vancomycin pulse-tapered regimen or oral fidaxomicin are considerations for all patients with two or more episodes of recurrent CDI.

A number of strategies for prevention of CDI and its recurrence have been investigated. In general, minimization of systemic antibiotic use and unnecessary proton pump inhibitor therapy is recommended.[1] In addition, handwashing for caregivers of all patients with CDI is critical to preventing transmission, as alcohol-based hand sanitizers do not kill C. difficile spores. Data regarding oral vancomycin for secondary prophylaxis among patients requiring systemic antibiotic therapy is conflicting, but there may be a lower rate of 90-day recurrence among patients with only one prior episode of CDI.[60] Studies of various probiotics have presented inconsistent results, with some demonstrating a greater risk of CDI recurrence with probiotic exposure.[1,61–65] In addition, probiotics appear to impair reconstitution of the gut mucosal microbiome after antibiotic use.[66] Therefore, probiotics are not recommended for CDI prophylaxis.

Bezlotoxumab is a monoclonal antibody that targets C. difficile toxin B that was approved in 2016 for the prevention of recurrent CDI among individuals at high risk of recurrence. In the MODIFY I/II phase 3 randomized controlled trials (RCTs), bezlotoxumab was associated with a significantly lower rate of recurrent CDI compared with placebo.[67] In a post-hoc analysis of high-risk subpopulations, a single infusion of bezlotoxumab resulted in a 27% absolute reduction in CDI recurrence within 12 weeks among patients with IBD. However, these results do not represent a statistically significant difference due to the relatively small number of IBD patients included in this analysis (28 randomized to bezlotoxumab, 14 randomized to placebo). Therefore, larger studies of bezlotoxumab are needed in the IBD population.[68]