What is the recommended treatment approach for Clostridium difficile (C. difficile) infection?

From the Guidelines

The recommended treatment approach for Clostridium difficile (C. difficile) infection is to use fidaxomicin 200 mg given twice daily for 10 days as the preferred treatment for initial episodes, and vancomycin 125 mg given 4 times daily by mouth for 10 days as an alternative, with adjustments made based on severity and recurrence status, as outlined in the 2021 focused update guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1.

Treatment Approach

The treatment approach for C. difficile infection varies depending on the severity and recurrence status of the infection.

• For initial episodes, fidaxomicin 200 mg given twice daily for 10 days is the preferred treatment, with vancomycin 125 mg given 4 times daily by mouth for 10 days as an alternative 1.
• For recurrent infections, extended vancomycin tapers, fidaxomicin, or fecal microbiota transplantation may be necessary, with bezlotoxumab 10 mg/kg given intravenously once during administration of standard of care antibiotics as an adjunctive treatment option for patients at high risk of recurrence 1.
• For severe or complicated infections, oral vancomycin 125-500 mg four times daily is recommended, with the addition of intravenous metronidazole 500 mg every 8 hours in fulminant cases 1.

Supportive Care

Supportive care for C. difficile infection includes:

• Fluid and electrolyte replacement
• Avoiding antimotility agents
• Discontinuing the inciting antibiotic if possible

Treatment Effectiveness

The effectiveness of these treatments stems from their ability to target C. difficile while minimizing disruption to the remaining gut microbiome, allowing restoration of normal intestinal flora that helps prevent recurrence 1. The most recent and highest quality study, the 2021 focused update guidelines by the IDSA and SHEA, provides the basis for these recommendations, prioritizing morbidity, mortality, and quality of life as the primary outcomes 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 recommended treatment approach for Clostridium difficile (C. difficile) infection is to use DIFICID (fidaxomicin) in adult and pediatric patients aged 6 months and older. The treatment should be used to treat infections that are proven or strongly suspected to be caused by C. difficile, and should be guided by culture and susceptibility information when available 2. Key considerations include:

• Using DIFICID only for treating C. difficile-associated diarrhea (CDAD)
• Selecting therapy based on local epidemiology and susceptibility patterns when culture and susceptibility data are not available
• Aiming to reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs.

From the Research

Treatment Approach for Clostridium difficile Infection

The recommended treatment approach for Clostridium difficile (C. difficile) infection includes:

• Oral metronidazole and vancomycin, although these treatments have limitations, including high rates of recurrence of infection 3, 4
• Fidaxomicin, a novel oral macrocyclic antibiotic that has shown superior clinical outcomes compared to vancomycin, with reduced rates of recurrence of infection 3, 4
• Other potentially effective strategies for recurrent C. difficile infection, including:
  • Tapering followed by pulsed doses of vancomycin
  • Use of other antibiotics such as nitazoxanide, rifaximin, tigecycline, and teicoplanin
  • Probiotics, fecal microbiota transplantation, intravenous immunoglobulin, monoclonal antibodies directed against C. difficile toxins, and active vaccination 5, 6

Management of Refractory or Recurrent C. difficile Infection

The management of refractory or recurrent C. difficile infection is challenging, and current guidelines recommend treating the first recurrence with the same agent used for the initial episode 5. However, data are lacking to support any particular treatment strategy for severe refractory C. difficile or cases with multiple recurrence.

Prevention of Downstream C. difficile Infections

Preventing downstream C. difficile infections with upstream antibiotic management is crucial, as selective pressure of antibiotic therapy can increase or lessen the risk of C. difficile infection 7. Formal studies evaluating the impact of antibiotic selection on the risk of subsequent C. difficile infection would be useful in this era of dangerous C. difficile.