Should a 16-year-old patient with a positive Clostridioides difficile (C. difficile) antigen test and a negative toxin test be treated for C. difficile infection?

From the Guidelines

A 16-year-old patient with a positive C. difficile antigen test but a negative toxin test should not be treated for C. difficile infection. This recommendation is based on the understanding that the presence of the antigen indicates colonization, while the absence of toxin suggests that the patient is not actively infected 1. The guidelines from the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) emphasize the importance of distinguishing between colonization and infection, as unnecessary treatment can disrupt the gut microbiome and potentially lead to further complications.

Key points to consider in this scenario include:

• The distinction between colonization and active infection, with the toxin test being critical for identifying disease-causing toxins.
• The potential for unnecessary antibiotic treatment to cause more harm than good, including disrupting the gut microbiome.
• The low yield of repeat testing within a short period, which is approximately 2% according to studies cited in the guidelines 1.
• The importance of investigating alternative causes of symptoms if they are significant or persistent.

Given the high negative predictive value of modern testing strategies, including NAATs, for CDI, a single negative toxin test in a patient with a positive antigen test but without clear signs of active infection (such as significant diarrhea or other supporting clinical evidence) does not warrant treatment for C. difficile infection. Instead, the focus should be on managing the patient's symptoms and investigating other potential causes, reserving repeat testing or empiric treatment for cases where clinical suspicion remains high despite initial negative findings 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Clostridioides difficile-Associated Diarrhea DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD).

1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile.

The patient is 16 years old, which is within the age range for treatment with fidaxomicin. However, the drug label does not provide direct guidance on treating patients with a positive antigen test and a negative toxin test.

• The label indicates the drug should be used to treat infections proven or strongly suspected to be caused by C. difficile.
• Since the toxin test is negative, it is unclear if the infection is proven or strongly suspected. Therefore, treatment should be approached with caution and consideration of additional diagnostic information or consultation with a specialist may be necessary 2.

From the Research

Treatment of C. difficile Infection

• The decision to treat a 16-year-old patient with a positive Clostridioides difficile (C. difficile) antigen test and a negative toxin test for C. difficile infection should be based on clinical judgment and the presence of symptoms 3.
• C. difficile infection is generally treated with vancomycin, metronidazole, or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults 4, 5.
• Studies have shown that FMT is effective in treating rCDI, with a large increase in resolution of rCDI compared to alternative treatments such as antibiotics 6, 7.

Diagnosis and Testing

• The diagnosis of C. difficile infection is typically made based on the presence of symptoms and a positive stool test for C. difficile toxin 3.
• The enzyme immunoassay (EIA) for toxin A and toxin B is a commonly used test, but it has sensitivity and specificity ranges of 50% to 90% and 70% to 95%, respectively 3.
• Repeat stool testing for C. difficile toxin may not be necessary, as the yield of repeat testing is low 3.

Treatment Considerations

• The treatment of C. difficile infection in pediatric patients may differ from that in adults, and the decision to treat should be based on individual clinical circumstances 4.
• FMT has been shown to be effective in treating rCDI in adults, but its use in pediatric patients is still being studied 4, 6, 7.
• The choice of treatment should be based on the severity of symptoms, the presence of underlying medical conditions, and the risk of recurrence 5, 7.