A 53-Year-Old Woman with Worsening Diarrhea during Treatment for Ulcerative Colitis: Practical Considerations in the Diagnosis of <i>Clostridioides difficile</i> Infection

<i>Clostridioides difficile</i> infection (CDI) poses a diagnostic challenge in patients with inflammatory bowel disease (IBD), as symptoms and endoscopic findings frequently overlap with those of disease flares, and asymptomatic colonization is relatively common. Consequently, positive microbiological test results do not always indicate active infection. We report the case of a 53-year-old woman with ulcerative colitis (UC) who presented with worsening bloody diarrhea and abdominal pain during maintenance therapy with infliximab. At initial admission, she had clinically significant diarrhea with elevated inflammatory markers. Stool testing demonstrated concordant positivity for glutamate dehydrogenase (GDH) antigen and toxin A/B enzyme immunoassay, supporting a diagnosis of active CDI concomitant with a UC flare. Treatment with oral vancomycin led to clinical improvement. Three weeks later, the patient re-presented with mild recurrent diarrhea. Repeat stool testing showed discordant results, including negative toxin A/B but positive GDH, polymerase chain reaction, and culture. Given the mild symptoms, normal inflammatory markers, and spontaneous symptom resolution without further antimicrobial therapy, these findings were interpreted as colonization or residual test positivity rather than recurrent CDI. This case illustrates key principles in CDI diagnosis: testing should be guided by the presence of clinically significant diarrhea, multistep diagnostic algorithms must be interpreted in the clinical context, and positive molecular or culture-based results in IBD patients do not necessarily reflect active infection. Symptom-based assessment is essential to avoid overdiagnosis and unnecessary antimicrobial treatment in patients with UC and suspected CDI.