ArticleThe Journal of antimicrobial chemotherapy2025
Decreased susceptibility to cefepime/zidebactam among carbapenemase-producing Escherichia coli from Stockholm, Sweden with alterations in PBP2.
Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Cefepime 2.0: Upgrading β-Lactamase Inhibitor Use.Microorganisms · 2026Review
- Characterizing the V516M penicillin-binding protein 2 (PBP2) mutation causing zidebactam resistance inAntimicrobial agents and chemotherapy · 2026Article
- Cefepime Combined with Late-Generation β-Lactamase Inhibitors: Mechanisms of Action, In Vitro Activity, PK/PD Characteristics, Clinical Evidence and Resistance Mechanisms.Antibiotics (Basel, Switzerland) · 2026Review
- Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Bacterial mutation dynamics emerging insights into virulence evolution and drug resistance. A review study.Frontiers in medicine · 2026Review
- Article
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4 authors.
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Abstract
objectivesWe aimed to investigate the in vitro activity and genetic determinants of decreased susceptibility (DS; MIC > 4 mg/L) to cefepime/zidebactam of carbapenemase-producing Escherichia coli.
methodsClinical isolates (N = 150) of carbapenemase-producing E. coli (CP-EC) belonging to seven distinct STs, isolated at a university clinical microbiology laboratory during 2019-2023 in Stockholm, Sweden were included. MICs for cefepime/zidebactam were determined using the broth microdilution method and interpreted using the tentative EUCAST clinical breakpoints (Susceptible; MIC < 4 mg/L; based on cefepime breakpoint). Whole genome sequences of the isolates were analysed with an emphasis on identifying alterations in PBPs 2 and 3.
resultsOf the 150 isolates, 145 (96.6%) isolates had MICs <4 mg/L indicating susceptibility and 5 (3.3%) had MICs >4 mg/L. MICs for zidebactam alone among the five isolates with DS to cefepime/zidebactam were ≥8 mg/L. WGS analysis revealed that these five isolates were NDM-5 producers and belonged to ST405 (n = 1), ST410 (n = 2) and ST648 (n = 2). Presence of four-amino-acid inserts (YRIK/YRIN) in PBP3 was observed in 80/150 (53.3%) isolates, and mutations leading to alterations in PBP2 were observed in 41/150 (27.3%) isolates. Presence of other β-lactamases (CTX-M group) and/or cephalosporinases (blaCMY) did not have an impact on the susceptibility to cefepime/zidebactam. Three of the five isolates with DS had a V522I substitution in PBP2.
conclusionsOur results indicate that DS to cefepime/zidebactam among clinical isolates of E. coli could arise due to targeted mutations in PBP2.
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