Abstract
Accurately diagnosing Clostridioides difficile infection (CDI) is crucial for effective patient management. A misdiagnosis poses risks to patients, leads to treatment delays, and contributes to infection transmission in healthcare settings. While using polymerase chain reaction (PCR) to amplify the toxin B gene is a sensitive method for detecting toxigenic C. difficile, there is still a risk of false-negative results. These inaccuracies could have significant consequences for diagnosing and treating CDI, emphasizing the need for careful consideration and other diagnostic approaches. This case report highlights a patient with severe CDI who had negative PCR and toxin and a biopsy showing pseudomembranous colitis on further testing due to persistence and worsening of symptoms. In the diagnosis of C. difficile infection, healthcare providers should consider clinical symptoms, although diarrhea, which is a major sign of CDI, can be due to other causes. Even in the presence of negative PCR results, if a patient displays symptoms consistent with C. difficile-associated disease, healthcare providers may still contemplate treatment.