In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes

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Title
In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes
Author(s)
Date
2024-11-06
Citation
Rodríguez-Pallares S, Blanco-Martín T, Lence E, Aja-Macaya P, Sánchez-Peña L, González-Pinto L, Rodríguez-Mayo M, Fernández-González A, Galán-Sánchez F, Beceiro A, González-Bello C, Bou G, Arca-Suárez J. In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes. Antimicrob Agents Chemother. 2024 Dec 5;68(12):e0130724.
Abstract
[Abstract] We describe the in vivo emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical Klebsiella aerogenes isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing revealed a differential mutation in AmpC (R148W) in the ceftazidime/avibactam-resistant isolate. Molecular cloning and structural studies confirmed the impact of this substitution, which affects the architecture of the H10 helix, on the evolved resistant phenotype.
Keywords
AmpC
Klebsiella aerogenes
Ceftazidime/avibactam
Evolution
β-lactamase
 
Description
Brief report
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Rights
Creative Commons Attribution 4.0 International License (CC-BY 4.0)
ISSN
0066-4804