Glucocorticoids are associated with increased risk of short-term mortality in hospitalized patients with clostridium difficile-associated disease

Abstract

Objectives: Glucocorticoids are commonly used to treat various illnesses in patients at risk for Clostridium difficile-associated disease (CDAD), but the effect of such immunosuppression on outcome has not been studied. We hypothesized that glucocorticoid use increases the risk of 30-day mortality in patients with CDAD.

Methods: We identified consecutive inpatients from 1 January 2004 to 30 September 2008, who had a positive Clostridium difficile toxin assay and recorded their demography, glucocorticoid usage before CDAD diagnosis, 30-day mortality, Charlson comorbidity score, and pertinent laboratory data. Three cohorts were created: Group 1: CDAD (+) without glucocorticoid use, Group 2: CDAD (+) with glucocorticoid use, and Group 3: CDAD (-) with symptomatic diarrhea and receiving glucocorticoids.

Results: Groups 1, 2, and 3 consisted of 841, 285, and 898 patients, respectively. Significant multivariate predictors of short-term mortality were age in Group 1 (P<0.001); age (P=0.007), Charlson score (P=0.004), and an endocrine indication for glucocorticoid use (P<0.01) in Group 2; and age (P<0.001), sex, (P=0.02), Charlson score (P<0.001), weight-adjusted glucocorticoid dose (1.10+/-0.03), and prednisone use (P<0.01) in Group 3. When considering all patients with CDAD (Groups 1 and 2), the use of any glucocorticoid resulted in an increased mortality with a hazard ratio of 2.1+/-0.19 (P<0.001). Mortality rates were 9.6%, 19.3%, and 9.7% for Groups 1, 2, and 3 (P<0.001 for Groups 1 and 3 vs. Group 2), respectively. Through Kaplan-Meier survival analysis, comparing the three groups revealed that patients with CDAD who received glucocorticoids were at significantly increased risk of short-term mortality compared with the control groups (Groups 1 and 3, P<0.001).

Conclusions: Mortality of patients with CDAD on glucocorticoids, regardless of the severity of CDAD, was significantly higher than the mortality of patients with CDAD not on glucocorticoids and those on glucocorticoids with symptomatic diarrhea and without C. difficile infection.