What is the recommended approach for diagnosing and treating Clostridioides difficile (C. diff) infection?

From the Guidelines

The diagnosis of Clostridioides difficile (C. diff) infection should be approached with a two-step algorithm using enzyme immunoassay for glutamate dehydrogenase followed by toxin testing, or nucleic acid amplification testing, as recommended by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) in their 2021 focused update guidelines 1. To diagnose C. diff, the following steps can be taken:

• Use a two-step algorithm with enzyme immunoassay for glutamate dehydrogenase followed by toxin testing
• Alternatively, use nucleic acid amplification testing The diagnosis is crucial in guiding the treatment approach, which depends on the severity and recurrence status of the infection. Treatment options for C. diff infection include:
• For initial mild to moderate cases: oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days is recommended 1
• For severe cases: oral vancomycin 125 mg four times daily for 10 days is preferred 1
• For fulminant C. diff: vancomycin 500 mg four times daily plus intravenous metronidazole 500 mg every 8 hours, with possible surgical consultation 1
• For first recurrence: use the same initial treatment if vancomycin was not used originally; otherwise, use a vancomycin taper and pulse regimen or fidaxomicin
• For multiple recurrences: options include vancomycin taper/pulse, fidaxomicin extended regimen, or fecal microbiota transplantation, with consideration of adjunctive treatment with bezlotoxumab 10 mg/kg given intravenously once during administration of standard of care antibiotics 1 Supportive care and prevention strategies are also essential in managing C. diff infection, including fluid replacement, avoiding antimotility agents, and discontinuing the inciting antibiotic if possible, as well as antimicrobial stewardship, contact precautions, and environmental cleaning.

From the FDA Drug Label

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. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

The diagnosis of C. diff infection is not explicitly described in the provided drug labels. However, it is mentioned that DIFICID should only be used to treat infections that are proven or strongly suspected to be caused by C. difficile. This implies that a diagnostic approach is necessary to confirm or suspect C. diff infection before initiating treatment with DIFICID.

• Key considerations for diagnosing C. diff infection include:
  • Culture and susceptibility information
  • Local epidemiology
  • Susceptibility patterns However, the exact diagnostic approach is not specified in the provided drug labels 2, 2, 2.

From the Research

Diagnosing C. diff Infection

• The diagnosis of Clostridioides difficile (C. diff) infection is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay 3.
• No single test is suitable as a stand-alone test confirming CDI, indicating that a combination of tests may be necessary for accurate diagnosis 3.

Treatment Approaches

• The antibiotics of choice for treating C. diff infection are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered inferior 3.
• Fidaxomicin has been shown to be effective in treating CDI, with some studies indicating it is superior to vancomycin for sustained response without recurrence 4, 5.
• However, other studies have found that fidaxomicin and vancomycin have similar rates of clinical cure and recurrence 6.
• The choice of treatment may depend on various factors, including the severity of the infection, the presence of concurrent infections, and the patient's medical history.

Considerations for Treatment

• Concomitant antibiotic use during the initial CDI episode is a major risk factor for recurrent CDI 6.
• Fidaxomicin has been associated with a lower risk of treatment failure compared to vancomycin in some studies 5, but other studies have found no significant difference between the two treatments 6.
• Metronidazole has been found to be inferior to fidaxomicin for initial episode treatment, but superior for recurrent CDI treatment in some studies 7.
• The resistance profile of C. difficile to vancomycin and metronidazole should be considered when choosing a treatment approach 7.