Discordant Clostridioides difficile testing as a predictor of inflammatory bowel disease therapy escalation

In patients with inflammatory bowel disease (IBD), Clostridioides difficile infection (CDI) presents with clinical features indistinguishable from the underlying disease. Sequential polymerase chain reaction (PCR) and enzyme immunoassay (EIA) testing reduce overdiagnosis; however, discordant results create management uncertainties.

We conducted a retrospective cohort study of IBD patients with positive C. difficile PCR testing at 2 institutions between April 2022 and December 2023. Patients were stratified by EIA toxin (TOX) results. Demographic, clinical, laboratory, and therapeutic data were extracted, and outcomes assessed included CDI-directed therapy or escalation of IBD treatment.

Of 575 IBD patients tested, 117 met inclusion criteria. Among them, 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 less likely to receive CDI treatment (72% vs 96%, P = .01) but 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; P = .045) and moderate-to-severe endoscopic disease within 1 year of testing (OR, 5.6; P = .0007) were significant predictors of IBD treatment escalation.

Elevated CRP may help distinguish true CDI in IBD. PCR+/TOX+ patients typically respond to CDI-directed therapy, whereas PCR+/TOX- patients more often require escalation of IBD treatment, suggesting noninfectious inflammation as the primary driver of symptoms.