What are the diagnostic tests for suspected Clostridioides difficile (C. Diff) infection?

From the Guidelines

For suspected Clostridioides difficile (C. diff) infection, testing should be performed on unformed stool samples using a two-step algorithm, first with a highly sensitive test like nucleic acid amplification test (NAAT), as recommended by the most recent guidelines 1. This approach is supported by the latest evidence, which emphasizes the importance of accurate diagnosis to guide treatment and prevent unnecessary antibiotic use. The two-step algorithm typically involves an initial screening with a sensitive test such as NAAT, followed by a toxin detection test to confirm active infection. Key points to consider in the diagnosis of C. diff infection include:

• Only test symptomatic patients with unexplained new-onset diarrhea (≥3 unformed stools in 24 hours) 1.
• Do not test formed stool, asymptomatic patients, or as a test of cure after treatment, as this can lead to false positives and unnecessary treatment 1.
• Collect a fresh stool sample in a clean container and transport it to the lab promptly to ensure accurate results.
• Testing should be considered for patients with diarrhea who have recently used antibiotics, are hospitalized, immunocompromised, or elderly, as these groups are at higher risk for C. diff infection 1.
• Empiric treatment with oral vancomycin or fidaxomicin may be initiated in severely ill patients while awaiting test results, but testing should always be completed before finalizing the diagnosis 1. It's also important to note that repeat testing after a first negative sample during the same diarrheal episode may be useful only in selected cases with ongoing clinical suspicion during an epidemic situation or in cases with high clinical suspicion during endemic situations 1. Overall, a careful and targeted approach to testing for C. diff infection is crucial to ensure accurate diagnosis and effective treatment, while minimizing the risk of unnecessary antibiotic use and promoting better patient outcomes.

From the Research

Suspected C. Diff Testing

• The diagnosis of Clostridium difficile infection (CDI) is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay 2.
• No single test is suitable as a stand-alone test confirming CDI, and diagnosis should be based on a combination of clinical criteria, microbiological tests, and endoscopy 3.
• Microbiological tests for CDI diagnosis include toxin tests, GDH antigen detection, PCR for toxin genes, and stool culture 3.
• Imaging techniques can be used to assess colonic inflammation and complications, such as pseudomembranous colitis (PMC) and toxic megacolon 3.
• The American Gastroenterological Association (AGA) and European guidelines emphasize integrating clinical and laboratory findings for accurate diagnosis of CDI 3.

Treatment Options

• The treatment of CDI involves stopping the implicated antibiotics and starting specific antimicrobial therapy, with common treatments including fidaxomicin and oral vancomycin 2, 3.
• Fecal microbiota transplantation (FMT) is recommended for recurrent cases unresponsive to standard treatments 2, 3.
• Bezlotoxumab, an antibody targeting C. difficile toxin B, is used to prevent recurrence in high-risk adults 3.
• Fidaxomicin has been shown to inhibit toxin production in C. difficile, which may explain its effectiveness in treating CDI 4.

Resistance and Challenges

• Antimicrobial resistance to treatments for CDI poses a significant threat to global health, and vancomycin resistance in C. difficile is a growing concern 5.
• The emergence of vancomycin resistance in C. difficile highlights the need for ongoing research and innovation in treatment options 5.
• A multifactorial approach involving rigorous preventive strategies, prudent antibiotic management, and adapted therapeutic options is essential for controlling CDI 3.