What are the diagnostic considerations for suspected Clostridioides difficile (C. diff) infection?

From the Guidelines

Suspected Clostridioides difficile (C. diff) infection requires prompt evaluation and treatment, with the most recent and highest quality study 1 guiding the approach to diagnosis and management. If C. diff is suspected, stool testing should be ordered immediately, typically using a two-step algorithm with glutamate dehydrogenase (GDH) antigen and toxin testing, or nucleic acid amplification testing (NAAT) as recommended by 1 and supported by 1. While awaiting results, discontinue any unnecessary antibiotics if possible. For diagnosis, a positive nucleic acid amplification test alone in the appropriate clinical context is also reasonable for making a CDI diagnosis, as stated in 1. Key considerations in the diagnosis include:

• The diagnosis of CDI should be based on clinical signs and symptoms in combination with laboratory tests, with stool testing limited to diarrheal stools from at-risk patients with clinically significant diarrhea, as emphasized in 1.
• Nucleic acid amplification tests (NAAT) for C. difficile toxin genes appear to be sensitive and specific and may be used as a standard diagnostic test for CDI, as noted in 1 and 1.
• Glutamate dehydrogenase (GDH) screening tests for C. difficile are sensitive but do not differentiate between toxigenic and non-toxigenic strains, and may be used in association with toxin A/B enzyme immunoassays (EIA) testing, as discussed in 1 and 1. For mild to moderate cases, oral vancomycin 125 mg four times daily for 10 days is the first-line treatment, as recommended by 1 and supported by 1. For severe cases, oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days is recommended, based on the guidelines provided in 1 and 1. In fulminant cases with hypotension or shock, use oral vancomycin 500 mg four times daily plus intravenous metronidazole 500 mg every 8 hours, as suggested by the treatment approaches outlined in 1 and 1. Metronidazole alone (500 mg three times daily for 10 days) may be used only for mild cases if access to vancomycin or fidaxomicin is limited, as noted in 1 and 1. Contact precautions should be implemented immediately, including hand washing with soap and water (alcohol-based sanitizers are ineffective against C. diff spores), to prevent the spread of C. diff, as emphasized in the examples and supported by the general principles of infection control. C. diff produces toxins that cause inflammation and damage to the colon, leading to symptoms ranging from mild diarrhea to life-threatening colitis, and recurrence occurs in about 20-30% of cases, which may require extended or pulsed antibiotic regimens, as discussed in the provided evidence 1.

From the FDA Drug Label

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.

5.3 Development of Drug-Resistant Bacteria Prescribing DIFICID in the absence of proven or strongly suspected C. difficile infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Treatment Indication: Fidaxomicin is indicated for the treatment of C. difficile-associated diarrhea (CDAD) in adult and pediatric patients aged 6 months and older.

• The drug should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile.
• In cases of suspected C. difficile infection, fidaxomicin may be prescribed, but it is essential to note that prescribing the drug in the absence of a proven or strongly suspected C. difficile infection increases the risk of developing drug-resistant bacteria 2, 2, 2.

From the Research

Diagnosis and Treatment of Suspected C. diff

• The diagnosis of C. diff is based on evidence of toxin, or the C. difficile organism itself, in a stool sample in the presence of clinical signs and symptoms 3.
• Only symptomatic patients should be tested for C. diff, and routine surveillance or repeat testing on asymptomatic patients as a test of cure is discouraged 3.
• The treatment of C. diff includes discontinuation of antibiotics, and the use of therapeutic agents such as metronidazole, vancomycin, and fidaxomicin 3, 4.

Treatment Options

• Fidaxomicin is a effective first-line treatment for C. diff infection, and has been shown to be noninferior to vancomycin in terms of clinical cure rates 5.
• Vancomycin is also a commonly used treatment for C. diff infection, and is often used in combination with fidaxomicin or as a taper and pulse regimen for recurrent infections 6, 4.
• Fecal microbiota transplantation is a highly effective treatment for recurrent C. diff infection, with a success rate of over 85% 6, 4.

Special Considerations

• Patients with inflammatory bowel disease may require special consideration when treating C. diff infection, and fidaxomicin has been shown to be effective in this population 7.
• The recurrence rate of C. diff infection is high, and patients may require multiple treatments or a combination of treatments to achieve a sustained clinical cure 5, 6, 4.
• The use of monoclonal antibodies, such as bezlotoxumab, may also be effective in reducing the rate of recurrence of C. diff infection 6, 4.