Jessica Allegretti, MD, on Tailored Treatment Strategies for C diff Infection and Recurrence in IBD

Clostridiodes difficile infection (CDI) remains the most common cause of health-care associated infection in the US,” explained Jessica Allegretti,  MD, at the Advances in Inflammatory  Bowel Diseases (AIBD) regional meeting on September 25.  “The scope of the problem in IBD is even larger, with a prevalence upward of 2.5-to 8-fold higher than non-IBD patients. Patients carry a 10% lifetime risk of infection.” 

Jessica Allegretti, MD, is associate director of the Crohn's and Colitis Center and director of the Fecal Microbiota Transplant program at Brigham and Women's Hospital in Boston, Massachusetts.

Dr Allegretti went on to describe the difficulties in diagnosing CDI among patients with IBD, as CDI presents with atypical features, including developing without antibiotic use, younger ages of infection, community onset, and patients lacking pseudomembranes.

“It’s important to remember the symptoms of these two diseases (CDI and IBD) really do overlap. We have diarrhea, fever, and abdominal pain being the most prevalent of symptoms, and so clinical differentiation can be quite difficult. And it’s for this reason that all patients presenting with IBD symptoms should be tested for C diff.” Dr Allegretti explained.

“So speaking of testing, I find this is often one of the more nuanced aspects of caring for these patients” Dr Allegretti began, and she continued to detail the possible tests for C diff. “The first test you may encounter is the antigen test … this is really a first pass screen, meaning are there any organisms present? The next test is the toxin test.” Dr Allegretti explained that while the toxin test has previously been unreliable, “I’m happy to report the newer version of this test we use is much more accurate.” However, she said, because of past reliability issues, many institutions moved to polymerase chain reaction (PCR)-only testing or DNA testing, or DNA toxin testing.

Dr Allegretti explained that PCR testing has its own shortcomings, which has caused her institution and many others to move to a 2-step testing approach, combining as a highly sensitive test such as glutamate dehydrogenase antigen (GDH) or PCR with a highly specific test like enzyme-linked immunosorbent assay (EIA) or toxin A/B).

“So how do we treat these patients? Again, there are several challenges in treating patients with C diff and IBD,” including

• Distinguishing active infection from flare
• Choice and duration of antibiotic therapy
• Escalation of de-escalation of immunosuppression
• Positioning fecal microbiota transplantation (FMT) in this patient population

Antibiotic treatments for initial CDI have included metronidazole and vancomycin. Prior to the year 2000, both treatments had identical failure rates (2.5% vs 3.5% respectively), but after 2000 the failure rate of metronidazole rose as high as 18.2. “That’s likely because we started to see the emergence of hypervirulent strains at this point,” Dr Allegretti explained. She went on to showcase the New Guidelines: IDSA 2018 chart, with clinical definitions, supportive data, recommended treatment, and strength of recommendation.

Fidaxomicin is also a recommended first-line agent for CDI, she said, but in a head-to-head study with vancomycin, the latter antibiotic showed better outcomes.

To date there are limited data about the treatment of CDI in patients with IBD because trials exclude these patients, she noted. What is known is that vancomycin can decrease colectomy rates, readmission, and length of stay among patients with IBD and C diff. Further, Dr Allegretti stressed, “IBD can be considered a CDI severity marker. I have always considered IBD to be a severity marker with regards to C diff; even if the patient is stable and an outpatient, I still treat them as if they have severe disease,” Dr Allegretti said.

“What is the current solution?” she continued. “Really you should be treating both. At no point should you be thinking that you need to stop treating the IBD to treat the C diff more effectively,” Dr Allegretti urged. She also explained the ACD clinical guidelines on CDI, including recommendations and key concepts, such as whether fecal microbial transplantation (FMT) should be considered.

With recurrent CDI— classified as the recurrence of symptoms after successful initial therapy for C. difficile within 8 weeks—risk factors include patient age, prior recurrent, antibiotic exposure, and again, IBD.

In discussing treatment for these patients, Dr Allegretti explained, “what we’ve learned from the guidelines is really that you want to be doing something different. If you used vancomycin initially, go to fidaxomicin. Do not repeat what you did the first course. By the time you are on your second recurrence, you really should be thinking about a vancomycin taper, or fidaxomicin if you haven’t used it. Bezlotoxumab should be used in conjunction with a course of antibiotics. And we are really talking about FMT at this point.”

Dr Allegretti explained that FMT “is the instillation of minimally manipulated microbial communities from stool of a healthy donor into a patient’s GI tract. And this is really how it is distinguished from a defined consortia of microbiotics, highlighting the degree of complexity of this therapy—and because of its complexity, the FDA considers this to be a biologic as well as a drug or tissue.”

Dr Allegretti further explained the guide for appropriate FMT use, beginning with patient selection and whether the treatment is appropriate; considering the donor and if it will be patient direct or universal; discussion and informed consent; delivery; and discharge and follow-up.

“With regard to COVID-19 and the pandemic, certainly how we practice, especially in this space, was significantly altered,” she said. W”hen the pandemic began, the FDA initially said any material produced after December 1, 2019, would not be eligible for use, but anything beforehand was fair game.” In July 2020,  the FDA rescinded this initial decision and required that all samples must be tested for COVID-19 for future use.

“There has been no transmission of COVID-19 through FMT to date,” Dr Allegretti said, adding, “So far we’re really not seeing any major safety signals,” Dr Allegretti reported.

“In conclusion, IBD patients are at increased risk for CDI, which can result in many disease sequela. Vancomycin or fidaxomicin are preferred over metronidazole, and immunosuppression may be continued and often actually needs escalation, and FMT is safe and effective, and should be offered for those patients,” Dr Allegretti stated.

—Angelique Platas

Reference

Allegretti J, Tailored treatment strategies for Clostridiodes difficile infection and recurrence in IBD. Presented at: Advances in Inflammatory Bowel Disease regional meeting. September 25, 2021. Virtual.