Corticosteroids Do Not Increase the Likelihood of Primary Clostridioides difficile Infection in the Setting of Broad-Spectrum Antibiotic Use

Abstract

Background: The pathogenesis of Clostridioides difficile infection (CDI) involves a significant host immune response. Generally, corticosteroids act by suppressing the host inflammatory response, and their anti-inflammatory effects are used to treat gastrointestinal disorders. Although previous investigations have demonstrated mixed results regarding the effect of corticosteroids on CDI, we hypothesized that the anti-inflammatory effect of corticosteroids would decrease the risk of CDI in hospitalized patients.

Methods: This was a case-control study of hospitalized adults. The case population included patients diagnosed with primary CDI who received at least 1 dose of a high-risk antibiotic (cefepime, meropenem, or piperacillin-tazobactam) in the 90 days before CDI diagnosis. The control population included patients who received at least 1 dose of the same high-risk antibiotic but did not develop CDI in the 90 days following their first dose of antibiotic. The primary study outcome was the development of CDI based on receipt of corticosteroids.

Results: The final study cohort consisted of 104 cases and 153 controls. Those who received corticosteroids had a lower odds of CDI after adjusting for age, proton pump inhibitor use, and antibiotic days of therapy (odds ratio, 0.54; 95% CI, 0.30-0.97; P = .04). We did not observe an association between corticosteroid dose or duration and CDI.

Conclusions: We demonstrated a 46% relative reduction in the odds of developing CDI in patients who received corticosteroids in the past 90 days. We believe that our results provide the best clinical evidence to further support mechanistic studies underlying this phenomenon.

Keywords: Clostridium difficile; antibiotic; corticosteroid; diarrhea; steroid.

Figure 1.

Multivariable logistic regression subgroup analyses. ^aOR represents relative odds for every 10-mg increase in the average daily dose of corticosteroid (measured using prednisone equivalents). ^bOR represents relative odds for every 1 DOT increase in the corticosteroid duration of therapy. ^cIncludes patients who received ≥20 mg of prednisone or equivalent per day for ≥2 weeks (n = 27) vs those who did not (n = 107). Abbreviations: DOT, days of therapy; OR, odds ratio; PPI, proton pump inhibitor.