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

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. DISCLOSURES: All authors: No reported disclosures.