<i>In vivo</i> emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in <i>Klebsiella aerogenes</i>
We describe the <i>in vivo</i> emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical <i>Klebsiella aerogenes</i> 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.
Authors
- Salud Rodríguez-Pallares (ORCID: https://orcid.org/0000-0002-8270-0259)
- Fátima Galán‐Sánchez (ORCID: https://orcid.org/0000-0003-0101-6701)
- Emilio Lence (ORCID: https://orcid.org/0000-0001-9489-9421)
- Concepción González‐Bello (ORCID: https://orcid.org/0000-0001-6439-553X)
- Alejandro Beceiro (ORCID: https://orcid.org/0000-0002-6340-7815)
- Ana Fernández-González (ORCID: https://orcid.org/0000-0002-7589-9052)
- María Rodríguez–Mayo
- Tania Blanco-Martín (ORCID: https://orcid.org/0009-0003-1636-6429)
- Pablo Aja‐Macaya (ORCID: https://orcid.org/0000-0001-6296-5949)
- Jorge Arca-Suárez (ORCID: https://orcid.org/0000-0002-4248-503X)
- Germán Bou (ORCID: https://orcid.org/0000-0001-8837-0062)
- Lucía González-Pinto (ORCID: https://orcid.org/0000-0002-8387-3784)
- Lucía Sánchez-Peña (ORCID: https://orcid.org/0009-0007-5696-5812)
Institutions
- Universidade de Santiago de Compostela (ES)
- Instituto de Salud Carlos III (ES)
- Center for Research in Molecular Medicine and Chronic Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- Biomedical Research and Innovation Institute of Cadiz (ES)
- Complexo Hospitalario Universitario A Coruña (ES)
- Hospital Universitario Puerta del Mar (ES)
- Instituto de Investigación Biomédica de A Coruña (ES)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2024-11-06
- DOI
- https://doi.org/10.1128/aac.01307-24
- Citations
- 4
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.68
Funders
- Pfizer
- European Commission
- Shionogi
- Axencia Galega de Innovación
- Xunta de Galicia
- Centro Singular de Investigación de Galicia
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación