What is the management of Clostridioides (C.) difficile infection following treatment for Salmonella infection?

From the Guidelines

For managing C. difficile infection following Salmonella treatment, the recommended approach is to start oral vancomycin 125 mg four times daily for 10-14 days, as per the guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1. This approach is based on the most recent and highest quality study available, which prioritizes the management of C. difficile infection to reduce morbidity, mortality, and improve quality of life.

Key Considerations

• Discontinue the antibiotic used for Salmonella if still being taken, as it likely contributed to the C. difficile infection by disrupting normal gut flora.
• Ensure adequate hydration and electrolyte replacement, particularly if the patient has significant diarrhea.
• Implement strict contact precautions to prevent transmission, including hand washing with soap and water rather than alcohol-based sanitizers, as C. difficile spores are resistant to alcohol.

Alternative Treatments

• Fidaxomicin 200 mg twice daily for 10 days can be used as an alternative, which has lower recurrence rates 1.
• For severe cases with complications like hypotension or ileus, increase vancomycin to 500 mg four times daily and add intravenous metronidazole 500 mg every 8 hours.

Recurrent Infections

• Consider fecal microbiota transplantation after appropriate antibiotic therapy, as suggested by the American Gastroenterological Association (AGA) 1.
• This approach targets the underlying cause of C. difficile overgrowth by restoring the normal intestinal microbiome that was disrupted by the antibiotics used to treat Salmonella.

Important Notes

• The use of fecal microbiota-based therapies should be considered on a case-by-case basis, taking into account the patient's immunocompromised status and other risk factors 1.
• The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials 1.

From the FDA Drug Label

14 CLINICAL STUDIES

Clinical Trials in Adults The safety and efficacy of ZINPLAVA were investigated in two randomized, double-blind, placebo-controlled, multicenter, Phase 3 trials (Trial 1 and Trial 2) in patients receiving Standard of Care antibacterial drugs for treatment of CDI (SoC) Randomization was stratified by SoC (metronidazole, vancomycin, or fidaxomicin) and hospitalization status (inpatient vs. outpatient) at the time of study entry. Enrolled patients were 18 years of age or older and had a confirmed diagnosis of CDI, which was defined as diarrhea (passage of 3 or more loose bowel movements in 24 or fewer hours) and a positive stool test for toxigenic C difficile from a stool sample collected no more than 7 days before study entry.

The management of Clostridioides (C.) difficile infection following treatment for Salmonella infection is not directly addressed in the provided drug labels.

• The labels discuss the treatment of CDI with bezlotoxumab (IV) 2 and fidaxomicin (PO) 3, but do not provide information on the management of CDI following treatment for Salmonella infection.
• Key points to consider in the management of CDI include the use of Standard of Care antibacterial drugs and the assessment of clinical cure and recurrence of CDI. However, without direct information on the management of CDI following treatment for Salmonella infection, no conclusion can be drawn.

From the Research

Management of Clostridioides difficile Infection

The management of Clostridioides difficile infection following treatment for Salmonella infection involves several approaches, including:

• Diagnosis using a two-step assay combining an enzyme immune assay for glutamate dehydrogenase and the C difficile toxin to reduce the risk of clinical false-positive results 4
• Treatment with fidaxomicin or vancomycin for a first episode of C difficile infection, with fidaxomicin being the preferred choice due to its higher success rate 4, 5, 6
• Management of recurrent C difficile infection using vancomycin taper and pulse or fidaxomicin, and consideration of intravenous bezlotoxumab to reduce recurrence rates 4, 5, 7
• Use of fecal microbiota transplantation as a rescue treatment for recurrent C difficile infection, with a success rate of over 85% 4, 5, 8

Treatment Options

The following treatment options are available for C difficile infection:

• Fidaxomicin: a first-line treatment for C difficile infection, preferred over vancomycin due to its higher success rate 4, 5, 6
• Vancomycin: an acceptable alternative to fidaxomicin, and used as a first-line treatment for C difficile infection 4, 5, 7
• Bezlotoxumab: a monoclonal antibody used to prevent recurrences of C difficile infection, particularly in patients at high risk 4, 5, 7
• Fecal microbiota transplantation: a rescue treatment for recurrent C difficile infection, with a success rate of over 85% 4, 5, 8

Prevention of Recurrence

To prevent recurrence of C difficile infection, the following strategies can be used:

• Use of vancomycin taper and pulse or fidaxomicin to manage recurrent C difficile infection 4, 5, 7
• Administration of intravenous bezlotoxumab to reduce recurrence rates in patients at high risk 4, 5, 7
• Consideration of fecal microbiota transplantation as a rescue treatment for recurrent C difficile infection 4, 5, 8