To the Editor Polage et al1 conclude that molecular tests should not be used as stand-alone diagnostic tests for Clostridium difficile infection (CDI), and clinical disease should be defined as a positive toxin result in patients with diarrhea. However, this neglects the major shortcoming of toxin assays that led to the development of molecular tests: toxin assays are insufficiently sensitive to detect all cases of clinically significant CDI. There are many documented instances in which toxin assays were negative in patients with severe CDI. One study2 found that even in patients with fulminant C difficile colitis, 12.5% had negative toxin assays, and the failure to make a laboratory diagnosis was associated with increased mortality. Polage et al1 noted a patient with a negative toxin immunoassay despite recurrent CDI that contributed to the patient's death, and a recent Swiss study3 of immunocompromised patients with CDI found equivalent in-hospital mortality and CDI recurrence rates in patients who were toxin assay positive (Tox+) or toxin assay negative (Tox−) and toxigenic culture positive.3 In the latter study, the toxin assay missed 43% of patients with CDI.
Fang FC. Toxin Immunoassays and Clostridium difficile Infection. JAMA Intern Med. 2016;176(3):412. doi:10.1001/jamainternmed.2015.8522