Diagnosis, Management, and Prevention of Recurrent C diff in Patients With IBD

Even as the treatment of inflammatory bowel disease (IBD) has advanced rapidly, the toll of the spore-forming anaerobic bacillus Clostridioides difficile has grown, Andrew DuPont, MD, told the attendees at the September 26 Advances in Inflammatory Bowel Disease virtual regional meeting.

Dr DuPont is an associate professor of gastroenterology, hepatology, and nutrition at the McGovern Medical School at the University of Texas Health Science Center in Houston, Texas.

From 2000 to 2010, hospitalizations for C diff infection (CDI) doubled, he said. As of 2011, the Centers for Disease Control and Prevention reported 453,000 cases of the infection in the United States, including 83,000 recurrences and 15,000 deaths, at a total cost of $40 billion. Mortality before 2000 was less than 2%; since that time, during endemic periods, the mortality of CDI has grown to 5%, advancing to 15% in epidemic periods. In cases of recurrent CDI, mortality increases by 33%, Dr DuPont stated.

“The risk of CDI is 5 times greater in patients with IBD,” he said. Most (85%) are community-acquired, and in only 20% of patients with IBD who contract the disease, CDI is associated with antibiotic use. “CDI is seen in up to 19% of patients with IBD during a flare,” Dr DuPont added, “and the risk increases with colonic involvement and the extent of IBD.” Steroid use increases the risk of CDI, he said.

In the mid-2000s an “epidemic strain” of CDI appeared, the PCR ribotype 027 and its North American pulsed field type1 (NAP1). This strain of the organism caused increased severity of the disease and mortality, and appears highly resistant to fluoroquinolones, Dr DuPont said. As fluoroquinolone use has decreased and infection control procedures have improved, the prevalence of this strain has also decreased.

However, CDI remains a serious risk for patients with IBD. “CDI increases the risk of subsequent flares and the need for therapy escalation,” Dr DuPont said. “Recurrent CDI raises the likelihood of subsequent emergency department visits, the risk of surgery, and mortality.” He noted that a 5-year mortality increased by 2.5 times among patients with IBD during and after hospitalization due to CDI.

He noted that guidelines from gastroenterological associations strongly recommend that all patients with IBD who present with a flare be tested for CDI.

Patients with IBD who are diagnosed with CDI should be treated with vancomycin (125 mg orally 4 times a day for 10 days) or fidaxomicin (200 mg orally 2 times a day for 10 days),

continued for a total of 14 days if the patient is still symptomatic at 10 days. While metronidazole was once a standard medication, it is now recommended for use only for nonsevere CDI when vancomycin or fidaxomicin are not available, dosed at 500 mg orally 3 times a day for 10 days. “Avoid repeat or prolonged exposure due to possible neurotoxicity,” when using metronidazole, Dr DuPont said.

In the general population, 25% of CDI recurrence occurs within 2 to 8 weeks, and most recurrences are due to relapses with the original strain, he explained. “If a patient has one recurrence, there is a 50% chance of a second recurrence; with a second recurrence, the risk of a third recurrence is 65%.”

Dr DuPont cited a study of 503 patients with CDI, including 110 patients with IBD (22%). Of the total cohort, 196 patients developed recurrent CDI, including 32% of the patients with IBD. The risk factors seen in the patients with IBD included recent use of antibiotics, 5-ASAs, steroids, and biologics, including infliximab but not adalimumab.

According to the Infectious Diseases Society of America guidelines, patients with IBD who have a first recurrence after a 10-day course of vancomycin should not be retreated with a second 10-day course of the antibiotic; there is a 36% chance of a second recurrence, Dr DuPont said. There is also a 20% chance of a second recurrence if a standard course of fidaxomicin is repeated. Instead, the recommendation is for a vancomycin taper followed by a pulsed regimen of 125 mg 4 times a day for 10 to 14 days, 125 mg 2 times a day for 1 week, 125 mg 1 time a day for 1 week, and 125 mg 1 time a day every 2 to 3 days for 2 to 8 weeks.

For a second or subsequent recurrence, the guidelines recommend a vancomycin taper and pulsed regimen; fidaxomicin; standard vancomycin followed by rifaximin; or fecal microbiota transplantation (FMT). Dr DuPont reviewed studies that showed the efficacy of rifaximin vs placebo in treatment of recurrent CDI.

He noted that a recent study of FMT in patients with IBD who had recurrent CDI showed that 92% had resolution of CDI, 64% of patients had improvement of their Crohn disease at week 12, 35% had no change in their Crohn disease, 57% of patients had improvement of their ulcerative colitis, 40% had no change, and 4% experienced a flare. There were no serious adverse events.

Recommendations now call for FMT to be considered after a second recurrence or third episode of CDI in patients with IBD. FMT is also indicated for first recurrence if the CDI requires hospitalization and in cases of fulminant CDI if there is no response to therapy after 48 hours.

—Rebecca Mashaw

Reference:

DuPont A. Diagnosis, management, and prevention of recurrence of C diff in the IBD patient. Talk presented at: Advances in Inflammatory Bowel Disease 2020 regional meeting; September 26, 2020; virtual.