Laboratory to Bedside: An Assessment of Clinical Outcomes in Adult Patients Receiving Definitive Cefazolin Therapy in Community-Acquired Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis Bacteremia Across MIC Breakpoints

Abstract

Background: In 2011, Clinical and Laboratory Standards Institute revised its systemic cefazolin minimum inhibitory concentration (MIC) breakpoints to address rising antibiotic resistance. The revision was based on pharmacokinetic-pharmacodynamic analysis with limited real-world data. Institutional review anticipated a shift from susceptible to intermediate sensitivity reporting with the new MIC breakpoints. This change may result in an increased use of broad-spectrum antibiotics in situations where cefazolin therapy would have been suitable in the past. Objective: The objective was to compare the rates of treatment failure in hospitalized adult patients with community-acquired monomicrobial Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis bacteremia with cefazolin MIC of ≤ 4 versus 8 μg/mL when treated with definitive cefazolin therapy. Methods: Single-centre, retrospective chart review of patients admitted to North York General Hospital between January 1, 2015 to December 31, 2022. Multivariable logistic regression was used to model treatment failure for MIC of ≤ 4 versus 8 μg/mL. Results: 2,018 charts were screened, and 280 patients met the inclusion criteria. 11 of 280 cultures had a MIC of 8 μg/mL. Patients with a MIC of ≤ 4 μg/mL received a higher proportion of ceftriaxone as empiric therapy (61% vs 27%, p<0.05) and had Escherichia coli as the predominant organism of interest (74% vs 36%, p<0.05). There was a non-significant increase in treatment failure in patients with a MIC of 8 μg/mL (OR 1.61, 95% CI [0.14-12.63], p=0.67). Conclusions: Consistent with existing literature, a trend towards higher treatment failure rates with MIC of 8 versus ≤ 4 μg/mL was identified. Future research should validate clinical outcomes in contemporary MIC breakpoints and investigate MIC susceptibility in gram-negative bacteremias from urinary sources.