124. Impact of Levofloxacin MIC on Outcomes with Levofloxacin Step-down Therapy in Enterobacteriaceae Bloodstream Infections

Abstract

Background. The Clinical and Laboratory Standards Institute reduced the levofloxacin minimum inhibitory concentration (MIC) breakpoint from ≤2 to ≤0.5 mg/L for Enterobacteriaceae in 2019 guidelines. The reduction is based on Monte Carlo simulations for a levofloxacin dose of 750 mg daily. The aim of this study was to determine whether there was a difference in clinical outcomes in the treatment of Enterobacteriaceae bacteremia with levofloxacin step‐down therapy retrospectively comparing patients with isolates with low levofloxacin MICs (≤0.5 mg/L) to high MICs (1‐2 mg/L). Methods. This retrospective, two‐center cohort study included patients ≥18 years of age with a monomicrobial Enterobacteriaceae bacteremia with a levofloxacin MIC ≤2 mg/L from March 2017 through December 2018. Patients had to have received treatment with ≥3 days of levofloxacin step‐down therapy, initial intravenous therapy with an agent active against the isolated organism, and total duration not exceeding 16 days from first negative blood culture. A subset of patients whose isolates had low levofloxacin MICs were randomly selected for comparison to all patients with high levofloxacin MICs in a 3:1 ratio. The primary outcome was a composite endpoint of recurrence and mortality within 30 days of completion of the antibiotic course. Secondary outcomes included post‐culture length of stay (LOS) and 30‐day readmission rate. Results. Thirty‐three patients with high MIC and 99 with low MIC were included. Urinary source was predominant and occurred in 44% of patients, and Escherichia coli was the infecting organism in 48%. Over 80% of patients experienced source resolution or control. The composite endpoint occurred in 8.1% of the low MIC group and 9.1% of the high MIC group (P = 0.856). Median LOS was 4.9 days (IQR 3.7‐8.0) in the low MIC group and 4.3 days (IQR 3.2‐6.8) in the high MIC group (P = 0.384), and readmission rate was 17.2% in the low MIC group and 15.2% in the high MIC group (P = 0.787). Conclusion. There was no between‐group difference in the primary outcome of recurrence and mortality, with a low overall event rate and short LOS post‐culture. These results suggest that levofloxacin effectiveness may be sustained in patients with MICs of 1 or 2 despite levofloxacin not meeting susceptibility criteria by new definitions.