P Ramakrishan et al. Inflamm Bowel Dis 2026; 32: 1313–1320. Discordant Clostridioides difficile testing as a predictor of inflammatory bowel disease therapy escalation

Background: “In the general population, individuals with discordant tests (PCR+/TOX−) have similar outcomes to PCR− individuals, suggesting that this group represents individuals colonized with C. difficile.[14]”

Methods: In this retrospective study (n=117), outcomes assessed included CDI-directed therapy or escalation of IBD treatment.

Key findings:

• 79% (93/117) were PCR⁺/TOX⁻ and 21% (24/117) were PCR⁺/TOX⁺
• PCR⁺/TOX⁺ patients had significantly higher CRP (98 vs 6 mg/L, P = .005)
• PCR⁺/TOX⁻ patients had more severe underlying IBD and higher rates of steroid use (48% vs 21%, P = .02) and were significantly more likely to require IBD therapy escalation (54% vs 25%, P = .004). Multivariable analysis showed PCR⁺/TOX⁻ status (odds ratio [OR], 3.2) was a significant predictor of IBD treatment escalation. Antibiotic use did not significantly alter the need for escalation among PCR⁺/TOX⁻  patients.

Discussion:

• “Most IBD patients who are PCR⁺/TOX⁻  are colonized with C. difficile, and IBD treatment could be considered rather than delaying for CDI therapy.”

My take: In patients with IBD, PCR-positivity for C diff is frequently a false positive due to high rates of colonization in this population. Patients who have their infection confirmed with an immunoassay are much more likely to respond to C diff therapy.

Related blog posts:

• Dr. Stacy Kahn: Clostridioides difficile 2026
• AGA Clinical Practice Update:  Clostridioides difficile Infection in Inflammatory Bowel Disease 12 best practice advice
• Overdiagnosis of Clostridium difficile with PCR Assays In a large adult study with 293 of 1416 hospitalized adults testing positive for C. diff, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method
• Clostridioides difficile Treatment in 2026
• Fidaxomicin Treatment of Clostridioides difficile in Children and Adolescents
• C difficile three-fer: Overdiagnosis with Multiplex Testing, Fidaxomicin Pediatric Approval, & Changing Incidence
• Clostridium difficile and Inflammatory Bowel Disease

Resources:

• CDC website has good information for families and clinicians.
• Peggy Lillis Foundation is another good website.
• For clinicians, a good pediatric review: DA Shirley et al. Pediatrics. 2023 Aug 10;152(3):e2023062307. doi: 10.1542/peds.2023-062307. Open Access! Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy