| Autor: |
Rajer F; Department of Medical Biochemistry and Microbiology, Uppsala Universitygrid.8993.b, Uppsala, Sweden., Allander L; Department of Medical Sciences, Uppsala Universitygrid.8993.b, Uppsala, Sweden., Karlsson PA; Department of Medical Biochemistry and Microbiology, Uppsala Universitygrid.8993.b, Uppsala, Sweden., Sandegren L; Department of Medical Biochemistry and Microbiology, Uppsala Universitygrid.8993.b, Uppsala, Sweden. |
| Jazyk: |
angličtina |
| Zdroj: |
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2022 Jun 21; Vol. 66 (6), pp. e0029022. Date of Electronic Publication: 2022 Jun 02. |
| DOI: |
10.1128/aac.00290-22 |
| Abstrakt: |
β-Lactam antibiotics are the first choice for the treatment of most bacterial infections. However, the increased prevalence of β-lactamases, in particular extended-spectrum β-lactamases, in pathogenic bacteria has severely limited the possibility of using β-lactam treatments. Combining β-lactam antibiotics with β-lactamase inhibitors can restore treatment efficacy by negating the effect of the β-lactamase and has become increasingly important against infections caused by β-lactamase-producing strains. Not surprisingly, bacteria with resistance to even these combinations have been found in patients. Studies on the development of bacterial resistance to β-lactam/β-lactamase inhibitor combinations have focused mainly on the effects of single, chromosomal or plasmid-borne, β-lactamases. However, clinical isolates often carry more than one β-lactamase in addition to multiple other resistance genes. Here, we investigate how the evolutionary trajectories of the development of resistance to three commonly used β-lactam/β-lactamase inhibitor combinations, ampicillin-sulbactam, piperacillin-tazobactam, and ceftazidime-avibactam, were affected by the presence of three common β-lactamases, TEM-1, CTX-M-15, and OXA-1. First-step resistance was due mainly to extensive gene amplifications of one or several of the β-lactamase genes where the amplification pattern directly depended on the respective drug combination. Amplifications also served as a stepping-stone for high-level resistance in combination with additional mutations that reduced drug influx or mutations in the β-lactamase gene bla CTX-M-15 . This illustrates that the evolutionary trajectories of resistance to β-lactam/β-lactamase inhibitor combinations are strongly influenced by the frequent and transient nature of gene amplifications and how the presence of multiple β-lactamases shapes the evolution to higher-level resistance. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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