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Impact of CLSI and EUCAST Cefepime breakpoint changes on the susceptibility reporting for Enterobacteriaceae
Jacqueline T Bork1, Emily L Heil2, Surbhi Leekha3
1University of Maryland School of Medicine, Department of Medicine, Division of Infectious Diseases, Baltimore, MD.
Objective:
We analyzed the effects of different cefepime MIC breakpoints on Enterobacteriaceae cefepime susceptibility and the presence of AmpC and extended-spectrum β-lactamase (ESBL) genes within the cefepime MIC interpretative categories.
Methods:
Using Enterobacteriaceae susceptibility data from 2013 comparisons of MIC breakpoints were performed using Pearson's chi-squared test. Molecular testing on a subset of isolates was done.
Results:
Among 3784 non-duplicate clinical isolates, cefepime susceptibility decreased from 97.6% to 96.1% to 93.7% for CLSI 2013, CLSI 2014, and EUCAST 2011, respectively. In ceftriaxone non-susceptible isolates, cefepime susceptibility decreased from 79% to 66% (P<0.0001) using CLSI 2013 and 2014, respectively, which was greater and statistically significant for Escherichia coli and Klebsiella spp. but not for Enterobacter spp. (P=0.06). Isolates with MIC ≤1μg/mL more often harbored AmpC (77%) than ESBL (18%) genes.
Conclusions:
Lower cefepime MIC breakpoints decrease cefepime susceptibility for isolates harboring ESBLs, while sparing the majority of those with AmpCs.
Insights
Lowering cefepime minimum inhibitory concentration (MIC) breakpoints reduces Enterobacteriaceae susceptibility, particularly for isolates with extended-spectrum beta-lactamase (ESBL) genes. This impacts cefepime effectiveness against common Gram-negative bacteria.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Cefepime is a crucial antibiotic for treating infections caused by Gram-negative bacteria.
- Changes in minimum inhibitory concentration (MIC) breakpoints can significantly alter antimicrobial susceptibility reporting.
- Enterobacteriaceae are a common cause of healthcare-associated infections, and their resistance patterns are a growing concern.
Purpose of the Study:
- To evaluate the impact of different cefepime MIC breakpoints on Enterobacteriaceae susceptibility.
- To determine the association between cefepime MIC interpretative categories and the presence of AmpC and extended-spectrum beta-lactamase (ESBL) genes.
- To assess how evolving breakpoint standards affect the interpretation of cefepime resistance.
Main Methods:
- Analysis of Enterobacteriaceae susceptibility data from 3784 clinical isolates.
- Comparison of cefepime MIC breakpoints using CLSI (Clinical and Laboratory Standards Institute) 2013, CLSI 2014, and EUCAST (European Committee on Antimicrobial Susceptibility Testing) 2011 guidelines.
- Molecular testing for AmpC and ESBL genes in a subset of isolates.
Main Results:
- Cefepime susceptibility decreased with progressively lower MIC breakpoints (97.6% to 93.7%).
- For ceftriaxone non-susceptible isolates, cefepime susceptibility dropped significantly from 79% to 66% with updated breakpoints (P<0.0001).
- Isolates with lower MICs (≤1 μg/mL) were more likely to harbor AmpC (77%) than ESBL (18%) genes.
Conclusions:
- Lower cefepime MIC breakpoints decrease reported susceptibility for Enterobacteriaceae, especially those with ESBL genes.
- The majority of isolates with AmpC genes remain susceptible even with tighter breakpoints.
- These findings highlight the importance of breakpoint selection in antimicrobial stewardship and resistance surveillance.