Syndromic panel testing among patients with infectious diarrhea: the challenge of interpreting Clostridioides difficile positivity on a multiplex molecular panel

Abstract Background Including Clostridioides difficile (CD) in gastrointestinal multiplex molecular panels (GIPCR) presents a diagnostic challenge. Incidental detection by PCR without consideration of pre-test probability may inadvertently delay diagnoses of other treatable causes of diarrhea and lead to prescription of unnecessary antibiotics. Methods We conducted a retrospective study to determine the frequency at which clinicians characterize pre-test probability (PTP) and disease severity in adult patients who test positive for CD by GIPCR. We organized subjects into cohorts based on the status of their CD PCR, glutamate dehydrogenase enzyme immunoassay (GDH), and toxin A/B detection, as well as by high, moderate, or low CD PTP. We used multivariable regression models to describe predictors of toxin positivity. Results We identified 483 patients with positive CD PCR targets. Only 22% were positive for both GDH and CD toxin. Among patients with a low PTP for CDI, 11% demonstrated a positive CD toxin result compared to 63% of patients with a high PTP. A low clinician pre-test probability for C. difficile infection (CDI) correlated with a negative CD toxin result compared to cases of moderate-to-high PTP for CDI (OR 0.19, CI 0.10-0.36). Up to 64% of patients with negative GDH and CD toxin received CD treatment. Only receipt of prior antibiotics, fever, and a moderate-to-high clinician PTP were statistically significant predictors of toxin positivity. Conclusions Patients with a positive CD PCR were likely to receive treatment regardless of PTP or CD toxin results. We recommend CD positivity on GIPCR be interpreted with caution, particularly in the setting of a low pre-test probability.