| Autor: |
Karoline Knudsen List, Mette Kolpen, Kasper Nørskov Kragh, Godefroid Charbon, Stine Radmer, Frank Hansen, Anders Løbner-Olesen, Niels Frimodt-Møller, Frederik Boetius Hertz |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Antibiotics, Vol 11, Iss 10, p 1280 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2079-6382 |
| DOI: |
10.3390/antibiotics11101280 |
| Popis: |
Background: Carbapenemase-producing Klebsiella pneumoniae and Escherichia coli have become a significant global health challenge. This has created an urgent need for new treatment modalities. We evaluated the efficacy of mecillinam in combination with either avibactam or ceftazidime/avibactam against carbapenemase-producing clinical isolates. Materials and methods: Nineteen MDR clinical isolates of K. pneumoniae and E. coli were selected for the presence of blaKPC, blaNDM, blaOXA or blaIMP based on whole-genome sequencing and phenotypic susceptibility testing. We tested the synergy between mecillinam and avibactam or ceftazidime/avibactam. We used time–kill studies in vitro and a mouse peritonitis/sepsis model to confirm the synergistic effect. We investigated avibactam’s impact on mecillinam´s affinity for penicillin-binding proteins with a Bocillin assay, and cell changes with phase-contrast and confocal laser scanning microscopy. Results: Mecillinam combined with ceftazidime/avibactam or avibactam substantially reduced MICs (from up to >256 µg/mL to |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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