Clinical Outcomes in Adult Patients Receiving Definitive Cefazolin Therapy for Community-Acquired Enterobacterales Bacteremias across Minimum Inhibitory Concentration Breakpoints.

Background: In 2011, the Clinical and Laboratory Standards Institute revised its minimum inhibitory concentration (MIC) breakpoints for systemic cefazolin therapy to address rising antibiotic resistance. The revision was based on pharmacokinetic-pharmacodynamic analysis with limited real-world data. Institutional review led to anticipation of a shift in classification for a substantial proportion of isolates from "susceptible" to "intermediate sensitivity". This change would result in increased use of broad-spectrum antibiotics in situations where cefazolin therapy would previously have been suitable. Objective: To compare the risk of treatment failure, as defined by mortality, intensive care admission, relapse bacteremia, and/or antimicrobial escalation, in hospitalized adult patients with community-acquired monomicrobial Methods: This single-centre, retrospective chart review involved patients admitted to North York General Hospital, Toronto, Ontario, between January 1, 2015, and December 31, 2022. Multivariable logistic regression was used to model and compare treatment failure for MIC ≤ 4 μg/mL and MIC of 8 μg/mL. Results: Of the 280 cultures eligible for analysis, 11 had MIC of 8 μg/mL, and the remaining 269 had MIC ≤ 4 μg/mL. For both groups, the treatment failure rate was 18.2%. With adjustment for confounding factors, there was a nonsignificant increase in the risk of treatment failure in patients with MIC of 8 μg/mL (odds ratio 1.29, 95% confidence interval 0.24-4.96, Conclusions: Consistent with the existing literature, this study showed a trend toward increased risk of treatment failure with higher MIC. Future research should validate clinical outcomes with contemporary MIC breakpoints and investigate MIC susceptibility in gram-negative bacteremia from urinary sources.