Diagnosing and Managing C diff in Patients With IBD

Diagnosing Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) “is one of the trickiest and most nuanced parts of caring for these patients,” because symptoms of CDI—diarrhea, abdominal pain, and fever—are very similar to those of an IBD flare, Jessica Allegretti, MD, said at the Advances in Inflammatory Bowel Disease virtual regional meeting on September 12.

Dr Allegretti is the codirector of the Crohn’s and Colitis Center at the Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts.

The prevalence of CDI in patients with IBD is between 2.5- and 8-fold higher than in patients without IBD, she explained. In addition, patients with IBD and CDI have a 4.5-fold higher risk of recurrent infection. The sequalae of CDI in patients with IBD can include serious complications, from loss of response to therapeutic agents to colectomy, additional recurrences of CDI, and higher mortality. This makes the rapid identification and effective treatment of CDI especially important.

Dr Allegretti emphasized, “All patients with IBD with worsening disease should be tested for CDI every time.” Patients with IBD who have CDI often do not fit the profile of the typical CDI patient, she said. These patients may be younger and may develop CDI while outside of the hospital.

Appropriate testing for CDI requires a 2-step process, she stated, beginning with a highly sensitive test such as glutamate dehydrogenase (GDH) or polymerase chain reaction (PCR) at the first step. If this test is positive for CDI, the next step should be a test with high specificity, such as enzyme-linked immunosorbent assay (EIA or ELISA), which has a high positive predictive value for toxins produced by C diff. If the first test is negative, the second test is not required; if the first test is positive, the second step will confirm the presence of CDI.

When treating patients with IBD for CDI, she said, “I cannot stress enough that you must treat your patients as if they have severe C diff—even an outpatient doing well.” The presence of IBD in a patient can be considered a marker of CDI severity in and of itself, she emphasized.

Further complicating the treatment landscape is the fact that the immunosuppressive drugs the patients with IBD often take “may worsen the underlying C diff infection but are required to manage a flare caused by CDI,” Dr Allegretti said. “You have to address both diseases. If you stop the immunosuppressives, the IBD is likely to get worse.”

The Infectious Diseases Society of America (IDSA) developed new guidelines for treating CDI in 2018, which set out recommended treatments for initial and recurrent episodes based on severity. Dr Allegretti emphasized that patients with IBD should always be treated according to the recommendations given for a severe case. For an initial episode, the IDSA guidelines recommend treatment with vancomycin, 125 mg, 4 times per day by mouth for 10 days or fidoxamicin, 10 mg, twice daily for 10 days. “Metronidazole no longer has any role in treating C diff,” she added.

Patients with IBD are also at higher risk of recurrent CDI, she noted. About 20% to 25% of patients with IBD who contract CDI will have a recurrent episode. “Each recurrence makes the next more likely,” she explained. “Age, antibiotic exposure, more virulent strains of C diff, and IBD with colitis are all risk factors for recurrent infection.”

“The big take home point on this issue is, do something different,” in the case of recurrence, Dr Allegretti stressed. “Switch antibiotics, use a prolonged taper with vancomycin.”

A new treatment, bezlotoxumab, is intended not to treat CDI but to prevent further recurrence. Dr Allegretti explained that bezlotoxumab “is a fully humanized monoclonal antibody that binds to C difficile toxin B. It’s indicated to prevent recurrence of CDI after a course of antibiotics has been administered.” Bezlotoxumab has been found to decrease recurrence rates of CDI by 10% overall, but by up to 25% in patients with IBD. “A single infusion of bezlotoxumab provided a 27.2% absolute reduction in the incidence of rCDI in participants with IBD (50% relative reduction).”

For continuing recurrence of CDI in patients with IBD, she said, “We’re really talking about fecal microbiota transplantation [FMT].” Although FMT is not approved by the US Food and Drug Administration, the agency exercises its enforcement discretion to permit the use of FMT in recurrent or refractory CDI, Dr Allegretti explained. It involves the “instillation of minimally manipulated microbial communities from stool of a healthy donor into a patient’s GI tract.”

In an open-label trial of FMT in 50 patients at 4 clinical sites, 4 participants out of 49 (8%) experienced CDI recurrence after FMT. Among participants with Crohn disease, 73.3% of participants (11 of 15) showed improvement in their IBD symptoms; 4 had no change in their clinical scores. Among participants with ulcerative colitis, 22 of 34 (62%) evidenced improvement in IBD symptoms, with 11 participants (29.4%) showing no change. Only 1 participant experienced a de novo flare of IBD.

“FMT has been shown to be very effective in treating CDI and preventing recurrent infection, with success rates of more than 90% in some studies,” Dr Allegretti said. “When a patient with IBD has multiple recurrences of CDI, FMT is safe and effective and should be offered.”

—Rebecca Mashaw

Reference:

Allegretti, JR. Clostridioides difficile infection in inflammatory bowel disease: diagnosis and management. Talk presented at: Advances in Inflammatory Bowel Disease 2020 regional meeting; September 12, 2020; virtual.