Evaluation of the clinical usefulness of C. difficile toxin testing in hospitalized patients with diarrhea

Although numerous studies have evaluated the sensitivity and specificity of different assays for Clostridium difficile toxin, none has evaluated how physicians utilize these tests or respond to test results. Therefore, we assessed patient characteristics, clinical findings, and physician responses to positive and negative assay results at two university-affiliated hospitals, one of which used a cell cytotoxicity assay to test for C. difficile toxin and the other of which used an enzyme immunoassay. Two hundred one patient samples at Hospital A and 199 samples at Hospital B were assessed. Positive toxin assays were more frequent at Hospital A than at Hospital B ( p < 0.001), at least in part due to the fact that patients tested at Hospital A were more likely to have fever ( p < 0.001), an abnormal abdominal exam ( p < 0.001), an abnormal leukocyte count ( p < 0.001), and a history of prior antibiotic use ( p < 0.001). Empiric therapy for C. difficile before results of the toxin assay was more common ( p < 0.001) at Hospital A (83/201, 41.3%) than at Hospital B (25/199, 12.5%). Once empiric therapy was started, most physicians continued therapy despite negative test results (Hospital A, 76%; Hospital B, 69%). Patients who were treated empirically were more likely than patients not treated empirically to have positive toxin assay results and to have fever ( p < 0.001), an abnormal abdominal exam ( p = 0.003), or an abnormal leukocyte count ( p < 0.05). Physicians seldom ordered repeat toxin assays (Hospital A, 14%; Hospital B, 10%) if the initial assay result was negative. In logistic regression analysis, predictors of a positive toxin assay were prior antibiotic therapy, an abnormal abdominal exam, residence at Hospital A, and age ≥ 60 years. Predictors of empiric therapy were residence at Hospital A and prior antibiotic therapy. Because physicians electing to empirically treat inpatients with diarrhea rarely alter therapy based on C. difficile toxin assay results, a more cost-effective management strategy may be not to obtain a toxin assay at all in such situations. Testing should be limited to patients who have received antibiotics within the prior month and who have significant diarrhea and/or abdominal pain.