Does a patient have Clostridioides difficile (C. diff) infection if they test positive for C. diff toxin deoxyribonucleic acid (DNA) but negative for C. diff toxin antigen, in the absence of diarrhea?

From the Guidelines

A patient does not have Clostridioides difficile (C. diff) infection if they test positive for C. diff toxin DNA but negative for C. diff toxin antigen in the absence of diarrhea. This testing pattern likely represents colonization rather than active infection, as supported by the study by Polage et al. 1, which found that patients who were toxin negative/PCR positive had similar rates of CDI-related complications and mortality as patients who were negative by both tests. C. diff infection is characterized by the presence of both the organism and its toxins, along with clinical symptoms, primarily diarrhea. The positive DNA test indicates the presence of the organism, but the negative toxin antigen suggests the bacteria are not actively producing toxins that cause disease. Without diarrhea, which is the hallmark symptom of C. diff infection, the patient is considered colonized but not infected. Some key points to consider in this scenario include:

• Colonization is common, especially in healthcare settings, and does not require treatment, as noted in the study by Planche et al. 1.
• Treating asymptomatic carriers is not recommended as it does not reduce transmission and may contribute to antimicrobial resistance.
• If the patient later develops diarrhea, reassessment would be warranted to determine if C. diff infection has developed, as suggested by the guidelines for Clostridioides difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1. The study by Polage et al. 1 provides the most recent and highest quality evidence to support this recommendation, as it is a large prospective observational cohort study that assessed the natural history and need for treatment of patients who were toxin EIA positive compared with toxin negative/PCR positive.

From the Research

C. diff Infection Diagnosis

• A patient testing positive for C. diff toxin DNA but negative for C. diff toxin antigen may not necessarily have a C. diff infection, as the presence of toxin DNA does not always indicate an active infection 2.
• The diagnosis of C. diff infection typically relies on a combination of clinical presentation, such as diarrhea, and laboratory tests, including stool toxin tests 3, 4.
• A two-step assay combining an enzyme immune assay for glutamate dehydrogenase and the C. difficile toxin is often used to diagnose C. diff infection, as it can help reduce the risk of clinical false-positive results with the polymerase chain reaction test 2.

Clinical Presentation and Diagnosis

• The clinical presentation of C. diff infection can range from mild diarrhea to fulminant infection requiring intensive care admission 2.
• Diarrhea is a common symptom of C. diff infection, but its absence does not rule out the possibility of infection 2, 3, 4.
• Laboratory tests, including stool toxin tests, are essential for diagnosing C. diff infection, but the results must be interpreted in the context of the patient's clinical presentation 3, 4.

Treatment and Management

• The treatment of C. diff infection typically involves antibiotics, such as vancomycin or fidaxomicin, and supportive care to manage hydration, electrolytes, and nutrition 2, 3, 5.
• In cases of recurrent C. diff infection, additional treatments, such as bezlotoxumab, a monoclonal antibody against the toxin B, may be recommended to reduce the risk of recurrence 2, 6.
• Fecal microbiota transplantation is also an option for patients with multiply recurrent C. diff infection, with a success rate of over 85% 2.