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美罗培南对……中接合性质粒转移的影响

Effect of Meropenem on Conjugative Plasmid Transfer in .

作者信息

Kondratieva Daria A, Savelieva Julia R, Golikova Maria V

机构信息

Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New Antibiotics, 11 Bolshaya Pirogovskaya Street, 119021 Moscow, Russia.

出版信息

Int J Mol Sci. 2024 Dec 8;25(23):13193. doi: 10.3390/ijms252313193.

Abstract

Plasmid-mediated resistance is a major mechanism that contributes to the gradual decline in the effectiveness of antibiotics from different classes, including carbapenems. Antibiotics can significantly contribute to the efficiency of plasmid transfer between bacterial strains. To investigate the potential effect of an antibiotic on the efficacy of conjugative plasmid transfer, we conducted mating experiments with strains. Donor strains of that carry plasmids with or carbapenemase genes and recipient plasmid-free strains were used in matings. Matings were conducted on the agar with or without meropenem at 1/8×, 1/4×, or 1/2×MIC against the respective recipients. In the second part of our study, we investigated the pharmacodynamic properties of meropenem against transconjugant strains of , which were obtained in the first part of this study. As a result, at a concentration equivalent to 1/8×MIC, meropenem primarily inhibited conjugation among strains, while at a concentration equal to 1/2×MIC, it facilitated conjugation. Transconjugants derived from with intermediate MICs failed to respond to simulated treatment with meropenem using prolonged infusion and a high-dose regimen. This finding suggests that such transconjugants may potentially pose a risk if involved in an infectious process.

摘要

质粒介导的耐药性是导致包括碳青霉烯类在内的不同类别抗生素有效性逐渐下降的主要机制。抗生素可显著促进细菌菌株间质粒转移的效率。为研究抗生素对接合性质粒转移效力的潜在影响,我们用菌株进行了交配实验。交配实验中使用了携带具有或碳青霉烯酶基因质粒的供体菌株以及无质粒的受体菌株。交配在含有或不含美罗培南的琼脂上进行,美罗培南浓度分别为针对相应受体的1/8×、1/4×或1/2×MIC。在我们研究的第二部分,我们研究了美罗培南对在本研究第一部分中获得的菌株的转接合子菌株的药效学特性。结果,在相当于1/8×MIC的浓度下,美罗培南主要抑制菌株间的接合,而在等于1/2×MIC的浓度下,它促进接合。来自具有中等MIC值的菌株的转接合子对使用延长输注和高剂量方案的美罗培南模拟治疗无反应。这一发现表明,如果此类转接合子参与感染过程,可能会构成风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fc9/11642842/a239280ec6db/ijms-25-13193-g001.jpg

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