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氟西汀和帕罗西汀与头孢曲松的抗菌协同作用、质粒DNA切割与重新定位

Antibacterial Synergism of Fluoxetine and Paroxetine with Ceftriaxone, Plasmid DNA Cleavage and Repositioning.

作者信息

Foletto Vitória S, Serafin Marissa B, da Mota Augusto D, da Rosa Taciéli F, Bottega Angelita, Marion Sara L, de Paula Bruno R, Franco Laísa N, Fuchs Luana B, Hörner Rosmari

机构信息

Programa de Pós-Graduação Em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.

Departamento de Análises Clínicas E Toxicológicas, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.

出版信息

Curr Microbiol. 2025 Jul 26;82(9):411. doi: 10.1007/s00284-025-04310-1.

DOI:10.1007/s00284-025-04310-1
PMID:40715552
Abstract

The indiscriminate use of antibiotics continues to promote a decrease in the sensitivity of bacteria to commercialized antibiotics. Current successful approaches, such as repositioning, enhance new uses for approved drugs. The antibacterial activity of fluoxetine (FX) and paroxetine (PX) combined with ceftriaxone (CTX) was evaluated against 5 standard strains and 72 multidrug-resistant clinical isolates collected in the years 2019 and 2021. FX showed minimum inhibitory concentrations (MIC) from 4 to 256 µg/ml and PX from 1 to 256 µg/ml, demonstrating that antidepressants showed better action than antibiotics (MIC from 512 µg/ml to > 4096 µg/ml). CTX had MIC reduced by 32 thousand times in combination with FX/PX. Antidepressants cleaved plasmid DNA by hydrolytic mechanism, demonstrating greater cleavage efficiency at pH 7.4 and temperature of 37 °C, that is, under physiological conditions. This is a demonstrative study of the promising action of FX/PX in combination with CTX in strains registered in 2019 and 2021, confirming it to be a promising alternative in antibacterial treatments.

摘要

抗生素的滥用持续促使细菌对商业化抗生素的敏感性降低。当前一些成功的方法,比如药物重新定位,为已获批药物拓展了新用途。评估了氟西汀(FX)和帕罗西汀(PX)与头孢曲松(CTX)联合使用对2019年和2021年收集的5种标准菌株及72株多重耐药临床分离株的抗菌活性。FX的最低抑菌浓度(MIC)为4至256微克/毫升,PX为1至256微克/毫升,这表明抗抑郁药的作用比抗生素更好(抗生素的MIC为512微克/毫升至>4096微克/毫升)。CTX与FX/PX联合使用时MIC降低了3.2万倍。抗抑郁药通过水解机制切割质粒DNA,在pH 7.4和37°C即生理条件下显示出更高的切割效率。这是一项关于FX/PX与CTX联合使用对2019年和2021年登记菌株的有前景作用的示范性研究,证实其为抗菌治疗中一个有前景的替代方案。

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本文引用的文献

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Drug-Repositioning Approaches Based on Medical and Life Science Databases.基于医学和生命科学数据库的药物重新定位方法。
Front Pharmacol. 2021 Nov 1;12:752174. doi: 10.3389/fphar.2021.752174. eCollection 2021.
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Repurposing of escitalopram oxalate and clonazepam in combination with ciprofloxacin and sulfamethoxazole-trimethoprim for treatment of multidrug-resistant microorganisms and evaluation of the cleavage capacity of plasmid DNA.草酸艾司西酞普兰和氯硝西泮与环丙沙星和复方磺胺甲噁唑联合再利用治疗多药耐药微生物及评估质粒 DNA 的裂解能力。
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Antibacterial activity of fluoxetine-loaded starch nanocapsules.
载氟西汀淀粉纳米胶囊的抗菌活性。
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Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis.COVID-19 患者的细菌合并感染和继发感染:一项实时快速综述和荟萃分析。
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Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study.85 例武汉 COVID-19 死亡病例的临床特征。一项回顾性观察研究。
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Molecules. 2020 Mar 4;25(5):1154. doi: 10.3390/molecules25051154.
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Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review.抗菌药物耐药时代对抗ESKAPE病原体的新兴策略:综述
Front Microbiol. 2019 Apr 1;10:539. doi: 10.3389/fmicb.2019.00539. eCollection 2019.
9
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Nature. 2016 Jun 16;534(7607):314-6. doi: 10.1038/534314a.
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