Role of Early De-escalation of Antimicrobial Therapy on Risk of Clostridioides difficile Infection Following Enterobacteriaceae Bloodstream Infections

Background: There is a paucity of data on the effect of early de-escalation of antimicrobial therapy on rates of Clostridioides difficile infection (CDI). This retrospective cohort study evaluated impact of de-escalation from antipseudomonal beta-lactams (APBL) within 48 hours of Enterobacteriaceae bloodstream infections (BSI) on 90-day risk of CDI. Methods: Adult patients hospitalized for >48 hours for treatment of Enterobacteriaceae BSI at Palmetto Health hospitals in Columbia, SC, USA, from January 1, 2011 through June 30, 2015 were identified. Multivariable Cox proportional hazards regression was used to examine time to CDI in patients who received >48 hours and ≤48 hours of APBL for empirical therapy of Enterobacteriaceae BSI after adjustment for the propensity to receive >48 hours of APBL. Results: Among 808 patients with Enterobacteriaceae BSI, 414 and 394 received >48 and ≤48 hours of APBL, respectively. Incidence of CDI was higher in patients who received >48 hours than those who received ≤48 hours of APBL (7.0% vs. 1.8%; log-rank p=0.002). After adjustment for propensity to receive >48 hours of APBL and other variables in the multivariable model, receipt of >48 hours of APBL (hazard ratio [HR] 3.38, 95% confidence intervals [CI]: 1.40-9.47, p=0.006) and end-stage renal disease (HR 4.04, 95% CI: 1.75-8.78; p=0.002) were independently associated with higher risk of CDI. Conclusions: The empirical use of APBL for >48 hours was an independent risk factor for CDI. Early de-escalation of APBL using clinical risk assessment tools or rapid diagnostic testing may reduce the incidence of CDI in hospitalized adults with Enterobacteriaceae BSI.