ArticleJournal of global antimicrobial resistance2025
Emerging resistance to novel β-lactam β-lactamase inhibitor combinations in Klebsiella pneumoniae bearing KPC variants.
Article in Journal of global antimicrobial resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
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Who cites it
9 citing papers in PubMed.
- Addressing therapeutic options for KPC-3-producing ST307-Antimicrobial agents and chemotherapy · 2026Article
- Repeated insertions at positions 261-280 in KPC-2 highlight a ceftazidime-avibactam resistance hotspot.iScience · 2026Article
- Characterization of KPC-160, a novel Ω-loop-deleted KPC variant on a dual-copy plasmid that confers cefiderocol resistance.Antimicrobial agents and chemotherapy · 2026Article
- Carbapenemases: epidemiology, detection and management in a changing global landscape.JAC-antimicrobial resistance · 2026Review
- Pharmacodynamic evaluation of BRII-693, a next-generation synthetic macrocyclic peptide antibiotic, in the neutropenic mouse thigh and lung infection models against gram-negative pathogens.Antimicrobial agents and chemotherapy · 2026Article
- DksA-Dependent Stringent Stress Response Drives Virulence and Gastrointestinal Persistence ofbioRxiv : the preprint server for biology · 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
- Article
- Spontaneous Emergence of Cefiderocol Resistance inAntibiotics (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
objectiveKlebsiella pneumoniae carbapenemase (KPC) variants, predominantly KPC-2 and KPC-3, are significant global resistance mechanisms, conferring resistance to many β-lactams, including carbapenems, while remaining susceptible to ceftazidime-avibactam (CZA). Recently, new KPC variants have developed resistance to CZA through mutations, insertions, or deletions in regions such as the Ω-loop, 240-loop (237-243 aa), and 270-loop (266-275 aa). This study investigated collateral resistance to cefiderocol (FDC) and cefepime/zidebactam (FPZ) in isolates with these mutations.
methodsFifteen clinical KPC-producing Klebsiella spp. isolates representing 15 distinct variants were analysed. Antimicrobial susceptibility testing determined the MICs for CZA, carbapenems, FDC, FPZ, and other antibiotics. Synergy between CZA and FDC was assessed. Whole-genome sequencing (WGS) was used to identify resistance-related mutations.
resultsCZA resistance was confirmed in 12/15 variants. Collateral resistance to FDC occurred in eight isolates, with five exhibiting spontaneous resistant subpopulations. Six FDC-resistant strains had mutations in the 270-loop (266-275 aa). FPZ resistance was seen in three KPC variants, especially those with mutations in the 270-loop, though many Ω-loop and 240-loop (237-243 aa) mutants remained susceptible. WGS of FDC-resistant subpopulations revealed additional mutations in ompC, rpoC, dksA, and cirA.
conclusionsEmerging CZA-resistant KPC variants often exhibit collateral FDC resistance, with FPZ seen less frequently. Mutations in bla
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.