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

We describe the emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing r...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2024-12, Vol.68 (12), p.e0130724
Main Authors: Rodríguez-Pallares, Salud, Blanco-Martín, Tania, Lence, Emilio, Aja-Macaya, Pablo, Sánchez-Peña, Lucía, González-Pinto, Lucía, Rodríguez-Mayo, María, Fernández-González, Ana, Galán-Sánchez, Fátima, Beceiro, Alejandro, González-Bello, Concepción, Bou, Germán, Arca-Suárez, Jorge
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antimicrobial Chemotherapy
Azabicyclo Compounds - pharmacology
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
beta-Lactamases - genetics
beta-Lactamases - metabolism
Ceftazidime - pharmacology
Drug Combinations
Drug Resistance, Multiple, Bacterial - genetics
Enterobacter aerogenes - drug effects
Enterobacter aerogenes - enzymology
Enterobacter aerogenes - genetics
Humans
Klebsiella Infections - drug therapy
Klebsiella Infections - microbiology
Mechanisms of Resistance
Microbial Sensitivity Tests
Mutation
Whole Genome Sequencing
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Summary:We describe the emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical 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.
ISSN:0066-4804
1098-6596
1098-6596
DOI:10.1128/aac.01307-24