Clostridioides difficile infection in inflammatory bowel disease: an observational study in flares of ulcerative colitis and a South Asian region-specific systematic review and meta-analysis

Background: Clostridioides difficile infection (CDI) is well-recognised as a cause of flare in inflammatory bowel disease (IBD). Objectives: To prospectively evaluate CDI as a cause of flare in moderate-to-severe ulcerative colitis (UC) and perform a region-specific systematic review to evaluate the role of CDI in IBD patients in South Asia. Design: A single-centre prospective observational study followed by a region-specific systematic review. Data sources and methods: The observational study was conducted between December 2024 and December 2025 and included patients with moderate-to-severe UC flares. Triple testing using Stool glutamate dehydrogenase (GDH), an enzyme immunoassay (EIA) for toxin A/B, and polymerase chain reaction (PCR) testing was performed. A literature search in PubMed, Embase, and Scopus was conducted on 5th December 2025 to identify relevant studies from South Asia. Information on the study population (IBD type, age, gender, disease activity), the testing method, and the outcomes of CDI testing were extracted. The pooled prevalence of CDI was estimated using a random-effects model. The risk of Bias was assessed using Joanna Briggs’ tool. Results: Of the 101 patients with active UC, 59 had acute severe UC. Six patients tested positive for GDH, whereas only one tested positive for EIA and PCR. A total of 13 studies reporting on 1267 patients were included in the systematic review. Pooled prevalence of CDI was 0.06 (0.03–0.11, I 2 = 80.8%). Subgroup analyses were performed by testing method, study type, and region. However, there was persistent statistical heterogeneity. Funnel plot and Egger’s test suggested the presence of publication bias. Conclusion: Our observational study shows a low prevalence of CDI as a cause of UC flares. The findings of the systematic review suggest high variability in the CDI positivity across South Asia. These differences were not fully explained by the method of testing, the type of study, or the geographic location of the study.