Clostridium difficile infection is often overdiagnosed in patients with mild diarrhea. We evaluated 4 biomarkers as surrogates for clinically significant diarrhea (≥ 3 episodes in 24 hours) in 59 PCR-positive patients with and 59 PCR-positive patients without clinically significant diarrhea. Organism burden (median tcdB cycle threshold value, 26.9 versus 27.1, P=0.25) and toxin A and B concentrations (toxin A, median, 0 versus 0 ng/mL, P=0.42; toxin B, median, 0 versus 0 ng/mL, P=0.25) were not significantly different between patients with and without clinically significant diarrhea. Fecal lactoferrin concentrations were significantly increased in patients with clinically significant diarrhea (median, 99.0 versus 55.1 μg/mL, P=0.05); however, lactoferrin could not sufficiently classify patients into those with and without clinically significant diarrhea. Interventions that limit C. difficile testing to patients with clinically significant diarrhea are needed to improve the positive predictive value of C. difficile diagnostics.
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