Treating C. difficile Infection in the IBD Population

Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI), which can result in a plethora of negative outcomes, said Jessica Allegretti, MD, MPH, at the Advances in Inflammatory Bowel Disease Regional meeting in Boston, Massachusetts.

Dr Allegretti is associate director of the Crohn’s and Colitis Center, and director of the Fecal Microbiota Transplant Program in the division of gastroenterology at Brigham and Women’s Hospital and Harvard Medical School.

Clostridioides difficile (C. diff) is the most common cause of health care-associated infection in the US. For patients with IBD, the prevalence is 2.5- to 8-fold higher than the general population, with a 10% lifetime risk, and a 4.5-fold higher risk of recurrence. Among patients with IBD, those with ulcerative colitis (UC) are at the highest risk. CDI in these patients can result in exacerbations of IBD, increased hospitalizations, increased length of stay, escalation in IBD therapy, colectomy, higher mortality rates, failure of CDI medical therapy, more CDI recurrences, and increased health care costs.

Further complicating matters, Dr Allegretti stated, “CDI presents with atypical features in IBD. ” It may develop without antibiotic use, it can present at a younger age, have community onset, and lack pseudomembranes. It is also common for colonization with infection to occur. Additionally, symptoms of CDI and IBD often overlap, with diarrhea being the most prominent symptom. With these difficulties, Dr Allegretti advised that “all patients with IBD presenting with worsening symptoms should be tested” for CDI.

The European Society of Clinical Microbiology and Infectious Diseases Guidelines state that no single commercial test can be used as a stand-alone for CDI testing. The recommendations are for either glutamate dehydrogenase or PCR testing first, followed by the enzyme immunoassay for toxin A/B.

Specific challenges in treating CDI within the IBD population include distinguishing active infection from disease flare, choosing the type and duration of antibiotic therapy, deciding whether to escalate/de-escalate immunosuppressive agents, and the positioning of fecal microbiota transplant (FMT). Since there is a lack of prospective data, providers are left having to extrapolate from non-IBD data.

While metronidazole and vancomycin were previously the treatments of choice for initial CDI, since 2000 the failure rates of metronidazole have risen from 2.5% to as high as 18.2%. Dr  Allegretti stated that that IBD can be considered a “CDI severity marker” and therefore CDI in a patient with IBD should be treated like severe disease, correlating to treatment with a course of either vancomycin or fidaxomicin.

While it has been previously thought that immunosuppression worsened the underlying infection, current American College of Gastroenterology guidelines recommend that immunosuppressive IBD therapy “should not be held during anti-CDI therapy in the setting of disease flare and escalation therapy may be considered if there is no symptomatic improvement of CDI.”

Recurrent CDI is a recurrence of C. diff symptoms after successful initial therapy within 8 weeks of resolution of symptoms from the previous episode. IBD with colitis is one of the risk factors for recurrent CDI. The treatment options for the first CDI recurrence are a vancomycin course if metronidazole was used initially, a prolonged taper of vancomycin, or a course of fidaxomicin. For a second or further recurrence, the options are a vancomycin taper, fidaxomicin, or potentially bezlotoxumab, a fully humanized monoclonal antibody that binds to C. diff toxin B and was found to decrease recurrence rates by 25% in patients with IBD.

Another option that Dr Allegretti described is FMT — an installation of minimally manipulated microbial communities from stool of a healthy donor into a patient’s gastrointestinal tract. Currently, the US Food and Drug Administration regulations allow for the use of FMT with no investigational new drug application for C. diff that is not responding to standard therapy, as long as the patient is informed that the treatment is investigational and the real and theoretical risks are discussed.

Dr Allegretti suggested consulting the 5Ds as a guide for appropriate FMT use: decision (is FMT appropriate?), donor (patient directed or universal?), discussion (informed consent), delivery (enema, colonoscopy/sigmoidoscopy, nasogastric/nasojejunal tube, capsules), and discharge (follow-up).

An appropriate candidate for FMT is a patient who has had ≥3 episodes of CDI with failure after a 6- to 8-week vancomycin taper, or a patient who has had ≥2 episodes of severe CDI resulting in hospitalization and significant morbidity. There are 2 models for obtaining the stool specimen: the patient-directed donor model, which requires a patient to identify a willing donor, and the stool bank model, in which a clinician orders preparations from a stool bank.

Acute concerns do exist with FMT, including the possibility of bacterial, viral, and parasitic infections, including the potential of a multidrug-resistant organism infection, or acute allergic reactions. Long term, it is unknown whether this procedure predisposes the recipient to diseases the donor may develop. Also, animal models suggest that microbiome plays a role in the pathogenesis of several human diseases (metabolic, heart, behavioral).

There are currently 4 randomized clinical trials exploring the use of FMT to treat IBD. In the study led by Dr Allegretti, she reported that 73.3% (11/15) of patients with CD and 62.2% (22/34) of patients with UC showed IBD improvement after treatment of FMT for CDI. Dr Allegretti stated that data from this trial showed that “the treatment was safer and better-tolerated than previously reported.”

In conclusion, Dr Allegretti reiterated that “IBD patients are at increased risk of CDI, which can result in many disease sequela” and that vancomycin and fidaxomicin are the preferred antibiotics over metronidazole for this population. She also noted that FMT is a “safe and effective” option for patients with IBD and recurrent CDI and that it “should be offered.”

—Allison Casey

Reference:

Allegretti J. Approach to C. difficile in 2022 and beyond. Presented at: Advances in Inflammatory Bowel Disease regional meeting; June 11, 2022. Boston, Massachusetts.