What is the management for a hospitalized patient with new onset diarrhea on antibiotics, with a Clostridioides difficile (C. diff) Polymerase Chain Reaction (PCR) positive but toxin negative result?

From the Guidelines

For a hospitalized patient with new onset diarrhea while on antibiotics who has a positive C. difficile PCR but negative toxin test, the recommended approach is to first discontinue the inciting antibiotic if clinically feasible. This patient likely has C. difficile colonization rather than active infection, as the negative toxin test suggests the organism is present but not producing disease-causing toxins. Close clinical monitoring without specific C. difficile treatment is appropriate for mild symptoms. If the diarrhea is severe or persists, oral vancomycin 125 mg four times daily for 10 days would be the first-line treatment, as recommended by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1. For patients with severe or complicated infection (marked by leukocytosis >15,000/μL, serum creatinine >1.5 mg/dL, or hypotension), more aggressive therapy with oral vancomycin 125 mg four times daily plus intravenous metronidazole 500 mg every 8 hours should be initiated.

Some key points to consider in the management of such patients include:

• The distinction between colonization and active infection is important because unnecessary treatment may disrupt gut microbiota further and potentially lead to antibiotic resistance.
• Supportive care including fluid replacement, electrolyte monitoring, and probiotics may be beneficial.
• Infection control measures including contact precautions should be implemented regardless of treatment decision to prevent transmission to other patients, as emphasized in guidelines for the management of Clostridioides difficile infection 1.
• Fecal microbiota transplantation (FMT) is an effective option for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments, with a high success rate in resolving diarrhea and preventing recurrence 1.
• The use of bezlotoxumab, a monoclonal antibody against C. difficile toxin B, may be considered for preventing recurrent CDI in high-risk patients 1.

Overall, the management of C. difficile infection, especially in hospitalized patients, requires careful consideration of the severity of the infection, the risk of recurrence, and the potential for transmission to other patients.

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 management of a hospitalized patient with new onset diarrhea on antibiotics, with a C. diff PCR positive but toxin negative result, is not directly addressed in the provided drug label. The label indicates that fidaxomicin is used to treat C. difficile-associated diarrhea (CDAD), but it does not provide guidance on the specific scenario of a toxin negative result.

• Key consideration: The presence of C. diff as indicated by PCR, even if toxin negative, may still require treatment due to the potential for progression to toxin-positive disease.
• Clinical decision: Treatment may be considered on a case-by-case basis, taking into account the clinical presentation, risk factors, and institutional guidelines, but the provided label does not directly support a specific management decision for this scenario 2.

From the Research

Management of C. diff Infection

The management of a hospitalized patient with new onset diarrhea on antibiotics, with a Clostridioides difficile (C. diff) Polymerase Chain Reaction (PCR) positive but toxin negative result, is a complex issue.

• The patient's symptoms and test results should be carefully evaluated to determine the best course of treatment.
• According to 3, fidaxomicin and vancomycin are two possible treatment options for C. diff infection, with similar efficacy and safety profiles.
• However, the patient's PCR positive but toxin negative result may indicate a carrier state rather than an active infection, which could affect treatment decisions.

Treatment Options

• Fidaxomicin has been shown to be effective in reducing the rate of recurrent C. diff infection 4.
• Vancomycin is also a commonly used treatment for C. diff infection, and has been shown to be effective in clinical trials 5.
• Metronidazole is another option, although it is considered inferior to vancomycin and fidaxomicin 6.

Considerations

• The patient's concomitant antibiotic use should be taken into account when selecting a treatment option, as some antibiotics may interfere with the efficacy of C. diff treatments 3.
• The patient's overall health status and medical history should also be considered when determining the best course of treatment.
• Symptomatic therapy, such as fluid and electrolyte replacement, may be necessary to manage the patient's symptoms, regardless of the treatment option chosen 4.

Diagnostic Evaluation

• A diagnostic evaluation, including a C. difficile toxin assay, should be performed to confirm the diagnosis and guide treatment decisions 7.
• The patient's response to treatment should be closely monitored, and adjustments made as necessary to ensure optimal outcomes.