Is it Clostridium difficile infection or something else? A case-control study of 352 hospitalized patients with new-onset diarrhea.

Background: Clostridium difficile-associated diarrhea (CDAD) is a leading cause of nosocomial diarrhea in the United States, and may be associated with significant morbidity and occasional mortality. Diarrhea is also very common among hospitalized patients and is often related to a variety of factors not related to C difficile infection.

Methods: We performed a retrospective case-control study at a tertiary care community medical center to delineate factors that are predictive of CDAD among hospitalized patients with new-onset diarrhea (ie, not present at the time of admission). Controls were selected based on negative C difficile toxin test(s) (CDTTs) (> 95% by cytotoxic assay), presence on the same ward as the patients with first positive CDTT, and hospitalization around the same period as the positive cases.

Results: The study involved 352 patients (88 cases and 264 controls). In univariate analysis, age 75 years or greater, exposure to cefazolin or levofloxacin during the 4-week period preceding CDTT, and hospitalization for 7 days or greater before CDTT were significantly associated with a positive test; male gender and prior ceftriaxone exposure nearly reached statistical significance. Multivariate logistic regression analysis revealed age 75 years or greater (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.3-3.7), hospitalization for 7 days or more (OR 2.3, 95% CI 1.3-3.8], and prior exposure to cefazolin (OR 3.5, 95% CI 1.6-7.5) or levofloxacin (OR 2.1, 95% CI 1.2-3.7) as independent predictors of a positive CDTT; male gender nearly achieved statistical significance (OR 1.6, 95% CI 0.9-2.7).

Conclusions: Among hospitalized patients with diarrhea who underwent testing for C difficile toxin, age 75 years or older, hospitalization for 7 days or greater, and recent exposure to cefazolin or levofloxacin were important predictors of a positive CDTT. These findings may help in the initiation of early presumptive treatment for CDAD, and appropriate isolation of higher risk patients before results become available. In addition, consideration of these risk factors may help in deciding whether a CDTT should be repeated when the first test is negative. Our study also supports more judicious use of antibiotics, particularly cefazolin and levofloxacin, in reducing the risk of CDAD in hospitalized patients.