| Summary: | The availability of highly sensitive molecular tests for the detection of <i>Clostridioides difficile</i> in feces leads to overtreatment of patients who are probably only colonized. In this prospective study, the usefulness of fecal calprotectin (fCP) is evaluated in a cohort of patients with detection of toxigenic <i>C. difficile</i> in feces. Patients were classified by an infectious diseases consultant blinded to fCP results into three groups—group I, presumed <i>Clostridioides difficile</i> infection (CDI); group II, doubtful but treated CDI; and group III, presumed <i>C. difficile</i> colonization or self-limited CDI not needing treatment. One hundred and thirty-four patients were included. The median fCP concentrations were 410 (138–815) μg/g in group I, 188 (57–524) μg/g in group II, and 51 (26–97) μg/g in group III (26 cases); <i>p</i> < 0.05 for all comparisons. In forty-five out of 134 cases (33.5%), the fCP concentrations were below 100 µg/g. In conclusion, fCP is low in most patients who do not need treatment against <i>C. difficile</i>, and should be investigated as a potentially useful test in the management of patients with detected toxigenic <i>C. difficile</i>.
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