Looking Beyond Clostridioides difficile: The Power of Syndromic Approach

When a patient presents with acute diarrhea, Clostridioides difficile is just one of several possible causes. The mariPOC CDI and Gastro combi test supports clinicians and laboratories to look beyond a single pathogen by providing broader and clinically more accurate diagnostic information from the same stool sample.

The researchers at Motol University Hospital in Prague set out to evaluate whether a multianalyte antigen test could provide additional diagnostic information when patient samples were initially referred for C. difficile testing.

The Challenge: Similar Symptoms, Different Causes

Diarrhea can be caused by a wide range of gastrointestinal pathogens. Yet when C. difficile infection (CDI) is suspected, laboratory diagnostics may initially focus on C. difficile alone. In such case, other potential pathogens may remain undetected. Additional challenges may also arise if the diagnostic method in use does not have high positive predictive value but may provide positive results despite the patient not having a CDI disease. These can create a diagnostic blind spot: what if the C. difficile finding is not the cause of the symptoms? Or is not the only pathogen involved? Tackling these challenges is easy when the laboratory aligns with the international guidance recommending the two-step diagnostic algorithm for C. difficile infection.¹

A study of 640 hospitalized patients with suspected C. difficile infection demonstrated the value of a broader diagnostic approach. In addition to detecting C. difficile, the mariPOC CDI and Gastro combi test identified 29 cases of other gastrointestinal pathogens that could otherwise have remained undiagnosed. These cases included 17 Campylobacter, 7 rotavirus and 5 norovirus GII.4 cases.

When a Positive C. difficile Result Is Not the Whole Answer

Among the patients studied, another gastrointestinal pathogen was identified in five samples with positive C. difficile GDH and negative free C. difficile toxin A/B results. Toxigenic cultures of these samples were positive, reflecting that the bacteria indeed carried toxin genes, but these genes were likely not expressed in the patient’s gut. Three of the samples were positive also for Campylobacter and two also for norovirus GII.4. These cases illustrate an important diagnostic challenge: a positive C. difficile screening result with culture, PCR or GDH immunoassay does not necessarily mean that C. difficile is the cause of the patient’s symptoms. Instead, a more specific method based on the detection of free toxin antigens is needed to rule in the diagnosis. Moreover, without broader testing, patients could have been directed towards C. difficile treatment while another clinically relevant pathogen remained unidentified.

More sensitive toxin detection

In the study, mariPOC demonstrated higher sensitivity for C. difficile toxin A/B antigens than the current market leading rapid immunoassay. Overall, mariPOC detected toxin A/B in 14 additional cases compared with rapid membrane enzyme immunoassay.

A Broader View of Gastrointestinal Infection

The study highlights the value of looking beyond the initially suspected pathogen. By combining the two-step C. difficile testing algorithm with detection of several other gastrointestinal pathogens from the same stool sample, mariPOC CDI and Gastro combi test provided additional diagnostic information that would otherwise have been missed.

Because sometimes the most important finding is the pathogen you were not originally looking for.

Reference: Krutova M, et al. Evaluation of a Gastrointestinal Pathogen Panel Immunoassay in Stool Testing of Patients with Suspected Clostridioides (Clostridium) difficile Infection. Journal of Clinical Microbiology. 2019;57(10).

¹ European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Crobach MJT, et al. Clin Microbiol Infect. (2016) Suppl 4S:63–81.