Clinical Impact of the Revised 2019 CLSI Levofloxacin Breakpoints in Patients with Enterobacterales Bacteremia.

BackgroundThe Clinical and Laboratory Standards Institute (CLSI) revised the fluoroquinolone minimal inhibitory concentration (MIC) breakpoints for Enterobacterales in 2019, based on pharmacokinetic/pharmacodynamic analyses. However, clinical evidence supporting these breakpoints revision is limited.MethodsA retrospective cohort was conducted at 3 hospitals in Taiwan between January 2017 and March 2019. Patients treated with levofloxacin for Enterobacterales bacteremia with high-MIC (1 or 2 μg/mL; levofloxacin-susceptible by pre-2019 CLSI breakpoints) were compared with those with low-MIC (≤0.5 μg/mL; levofloxacin-susceptible by 2019 CLSI breakpoints) to assess therapeutic effectiveness in multivariable logistic regression. The primary outcome was 30-day mortality and the secondary outcome was the emergence of levofloxacin-resistant isolates within 90 days after levofloxacin initiation.ResultsA total of 308 patients were eligible in the study. Kaplan-Meier analysis showed that patients infected with high-MIC isolates (n=63) had a significantly lower survival rate compared with those infected with low-MIC isolates (n=245) (p=0.001). Multivariable logistic regression revealed high levofloxacin MIC was a predictor of 30-day mortality [odds ratio (OR) 6.05, 95% confidence interval (CI) 1.51-24.18, p=0.011]. We consistently found similar result in propensity-score matched cohort (OR 5.38, 95%CI 1.06-27.39, p=0.043). The emergence of levofloxacin-resistant isolates was likely more common in the high-MIC group compared to the low-MIC group (7.5% vs. 25.0%, p=0.065). An estimated AUC/MIC ratio≥ 87 was significantly associated with better survival (p=0.002).ConclusionsPatients with high levofloxacin MICs within the pre-2019 CLSI susceptible range of 1 or 2 μg/mL were associated with higher mortality compared to those with MICs ≤0.5 μg/mL.