Experts at IDWeek 2025 emphasized that diagnosing Clostridioides difficile infection (CDI) now requires greater clinical judgment, as highly sensitive molecular tests can detect bacterial colonization without confirming active disease. While PCR-based nucleic acid amplification tests (NAATs) are excellent at identifying C. difficile, they may overdiagnose infection if used indiscriminately. Clinicians were advised to reserve testing for patients with genuine, profuse watery diarrhea, typically six or more stools per day, rather than relying solely on laboratory results.
Dr. Javier A. Villafuerte Gálvez of Beth Israel Deaconess Medical Center noted that certain symptom patterns should prompt consideration of alternative diagnoses. Intermittent diarrhea, normal stools between episodes, or diarrhea that resolves overnight are generally inconsistent with symptomatic CDI. He stressed that laboratory testing should always be interpreted within the broader clinical context, as no single test can definitively distinguish colonization from active infection.