According to a new AGA clinical practice update, patients with inflammatory bowel disease (IBD) who develop Clostridioides difficile infection should receive fidaxomicin as the preferred first-line treatment, continue any necessary immunosuppressive therapy, and be considered for microbiome-based therapies if the infection recurs.
The expert review, published in Gastroenterology, provides 12 best practice recommendations for managing Clostridioides difficile infection (CDI) in people with inflammatory bowel disease (IBD), who face a higher risk of infection, more severe illness, and more frequent recurrences than those without IBD. The authors noted that CDI symptoms often resemble an IBD flare, making diagnosis and treatment more challenging.
“This is a very timely update as the management of CDI in patients with IBD continues to be both common and complex,” one of the review’s authors, Sahil Khanna, MBBS, MS, a consultant in the division of gastroenterology and hepatology in the department of internal medicine at Mayo Clinic, Rochester, Minnesota, told GI & Hepatology News. “Patients with IBD are at a higher risk for CDI despite lack of exposures to antibiotics, and have higher rates of hospitalization, recurrences, escalation or failure of IBD therapy, and surgery. Clinically, CDI and an IBD flare can look very similar, yet the treatments differ.”
The update was commissioned by the AGA Institute Clinical Practice Updates Committee and based on a review of published studies, systematic reviews, guidelines, and expert opinion rather than a formal systematic review.
The authors recommend testing all patients with IBD who develop new or worsening diarrhea for CDI, especially those with disease affecting the colon. Patients with ileostomies or ileal pouch-anal anastomoses should also be tested if stool output increases, because CDI has been reported in 10% to 18% of patients with pouch disorders.
People with IBD are up to eight times more likely to develop CDI than the general population, even without recent antibiotic use, the authors noted. They also face a much higher risk of recurrence, with a 33% greater chance of recurrent infection compared with people without IBD.
To help distinguish active infection from harmless colonization, the update recommends using a multistep, toxin-based testing approach instead of relying on polymerase chain reaction testing alone. The preferred method begins with glutamate dehydrogenase or nucleic acid amplification testing, followed by a toxin enzyme immunoassay to confirm the diagnosis. A positive polymerase chain reaction test combined with a negative toxin test may suggest colonization rather than an active infection, the authors said.
For treatment, fidaxomicin was favored over vancomycin because of lower recurrence rates and reduced disruption of the intestinal microbiome. Cure rates with fidaxomicin in retrospective IBD studies were reported at about 80% to 90%.
The review also cited a phase IIIb/IV pharmacokinetic study showing minimal systemic absorption of fidaxomicin in patients with IBD and high stool drug concentrations. In another randomized trial involving older hospitalized patients without IBD, extended-pulsed fidaxomicin achieved sustained clinical cure in 70% of patients compared with 59% for vancomycin.
Vancomycin remains an acceptable alternative when fidaxomicin is unavailable or cost-prohibitive, but metronidazole should no longer be used because of high resistance and treatment failure rates, according to the update. The authors also highlighted evidence supporting longer vancomycin regimens lasting 21 to 42 days in patients with IBD to reduce recurrence risk.
The update’s authors advise physicians to strongly consider hospitalization for patients with IBD and CDI who develop severe colitis, systemic toxicity, or sepsis. Warning signs include more than six bowel movements daily, severe abdominal pain, leukocytosis, hemodynamic instability, or toxic megacolon. CDI in patients with IBD has been associated with increased in-hospital mortality.
Dr. Khanna and colleagues also discussed immunosuppressive therapy, noting that no specific class of biologic or small-molecule drugs has been linked to a higher risk for CDI. Physicians should choose therapies based on the patient’s IBD treatment needs rather than concerns about increased CDI risk. Retrospective studies also suggested that continuing or intensifying immunosuppressive therapy during CDI treatment does not worsen infection outcomes when clinically appropriate.
If symptoms continue after 48 to 72 hours of CDI treatment, the update recommends endoscopic evaluation to look for ongoing IBD activity or other possible causes, such as cytomegalovirus infection. The authors also noted that pseudomembranes are uncommon in patients with both IBD and CDI, which can make diagnosis more difficult.
Among the most notable recommendations was strong support for microbiome-based therapies after recurrent CDI. The authors advised offering fecal microbiota transplantation or US Food and Drug Administration-approved microbiota restoration products after at least one recurrence.
Data cited in the review showed fecal microbiota transplantation achieved 90% efficacy at eight weeks in one prospective trial involving patients with IBD and recurrent CDI. Another phase III open-label study of fecal microbiota, live-jslm reported a 79% treatment success rate at eight weeks and a sustained clinical response rate of 91% at six months among patients with IBD.
The authors do not recommend probiotics for preventing initial or recurrent CDI because evidence of benefit is limited and they may pose risks, including bloodstream infections, in immunocompromised patients.
The review noted that oral vancomycin prophylaxis may be considered for secondary prevention in high-risk patients with prior CDI who require systemic antibiotics, although supporting evidence remains limited.
According to Dr. Khanna, he and his coauthors spent considerable time discussing how to manage immunosuppressive therapy during active CDI. “Clinicians are appropriately concerned about worsening CDI, but uncontrolled IBD can also lead to hospitalization, surgery, and other poor outcomes,” he said. “The evidence base is retrospective, and randomized trials are lacking.”
Another area that required careful discussion, Dr. Khanna said, was microbiome-based therapy in IBD, particularly as the field has moved from conventional FMT toward FDA-approved donor-derived therapies. “We now have more options, but the data are uneven across products and across IBD subgroups,” he said. “We also spent time on oral vancomycin prophylaxis because it is used in real-world practice, but the evidence remains low quality and must be weighed against concerns such as vancomycin-resistant Enterococcus carriage.”
Dr. Khanna reported research support from Vedanta Biosciences and consulting relationships with several pharmaceutical companies. Jessica R. Allegretti, MD, MPH, Jana G. Hashash, MD, MS, and Paul Feuerstadt, MD, reported advisory, consulting, or speaking relationships with multiple industry companies, including Ferring Pharmaceuticals, Janssen Pharmaceuticals, Takeda Pharmaceuticals, and others.
Expert Insight
GI & Hepatology News invited one of the review’s authors, Sahil Khanna, MBBS, MS, a consultant in the division of gastroenterology and hepatology in the department of internal medicine at Mayo Clinic, Rochester, Minnesota, to elaborate on the update.
In your opinion, what are the top 2-3 best practice advice statements from this review?
Dr. Khanna: The first is the paired message that best practice advice 1 and 2 have. Any IBD patient with new or worsening diarrhea should be tested for CDI, with a multistep toxin-based strategy. This also applies to patients with an ileal pouch or end ileostomy who develop worsening output.
The second is best practice advice 4: for an initial episode of CDI in IBD, fidaxomicin should be preferred when feasible, with oral vancomycin as an appropriate alternative if fidaxomicin is not available or is cost prohibitive. Metronidazole should not be used.
The third is best practice advice 7 and 10 together. We should not reflexively undertreat IBD because CDI is present; concurrent treatment of IBD is often necessary, including continuation of needed immunosuppressive therapies. At the same time, patients with IBD who have at least one CDI recurrence should be offered microbiome-based therapy to prevent future infection. Those two statements reflect the central theme of the update: treat CDI effectively, and do not lose control of the underlying IBD.
Are there specific best practice advice statements in the update that surprised you?
Dr. Khanna: A few may surprise clinicians. Best practice advice 9, which suggests using loperamide in selected patients, challenges a long-standing reflex to avoid antimotility agents in CDI under all circumstances. This is suggested for patients whose infection and inflammation are improving, who are already on appropriate CDI therapy, and who do not have fulminant disease or systemic toxicity.
Best practice advice 6 would be reassuring to clinicians. Based on the available evidence, IBD therapy should not be selected primarily on the basis of perceived CDI risk by drug class. The choice should be driven by what best treats the patient’s IBD.
Did any aspect of your clinical practice change because of helping to form this update?
Dr. Khanna: The update reinforces and formalizes several aspects of the authors’ clinical practice. We are more deliberate about diagnostic stewardship: in an IBD patient with worsening diarrhea, a positive PCR alone is not enough to assume active CDI. A toxin-based multistep approach and careful clinical interpretation are essential.
It also reinforces a more proactive approach to recurrence prevention. In patients with IBD, we consider fidaxomicin for an initial episode when feasible, and have a lower threshold to discuss microbiome-based therapy after a recurrence. Just as importantly, we do not reflexively stop needed IBD therapy. The better approach is to treat CDI promptly, reassess early, and escalate IBD evaluation or therapy when the patient is not improving within 48 to 72 hours.
Is there anything else you’d like to say about this work?
Dr. Khanna: The main message is that CDI in IBD requires careful diagnostic interpretation, prompt CDI-directed treatment, ongoing attention to IBD activity, and a plan to prevent recurrence. The update addresses common bedside questions, such as how to test, what antibiotic to choose, when to hospitalize, whether to continue immunosuppression, when to scope, whether loperamide is ever appropriate, and when to use microbiome-based therapies.
We hope the update reduces therapeutic hesitation. These patients do poorly when either side of the problem is neglected. The best outcomes come from treating both conditions thoughtfully and reassessing early when the clinical course does not make sense.