重新定位的药物和排泄抑制剂对抗阴性尿道病原性细菌
Annamária Kincses1,2, Márta Nové1, Jina Asefi1
1Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary.
Antibiotics (Basel, Switzerland)
|October 28, 2025
概括
重用药物和排泄抑制剂 (EPI) 在通过抑制细菌生物膜和提高抗生素有效性来对抗抗生素耐药性尿道感染 (UTI) 方面表现有前途.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
背景情况:
- 尿路感染 (UTI) 由于抗菌素耐药性增加和细菌生物膜形成的挑战,造成了严重的医疗负担.
- 像*Escherichia coli*,*Klebsiella pneumoniae*和*Proteus mirabilis*这样的グラム阴性泌尿病原体是尿路感染的常见原因,并且经常表现出抵抗机制.
- 开发替代策略来对抗抗性尿路感染至关重要,探索新的治疗剂和组合.
研究的目的:
- 评估重新定制药物和排泄抑制剂 (EPI) 的抗菌,抗生物膜和耐药性修饰性质.
- 在与尿路相关的各种pH条件下,对关键的格拉姆阴性尿病原体研究这些特性.
- 评估这些药物作为常规抗生素辅助剂的潜力,用于治疗耐药性尿路感染.
主要方法:
- 针对pH值为5-8的临床分离物,对 thioridazine (TZ),promethazine (PMZ),fluoxetine (Fx),sertraline (Sr),phenylalanine arginine β-naphthylamide (PAβN),碳酸m-chlorophenyl hydrazone (CCCP) 和V9302的最小抑制度 (MIC) 进行了确定.
- 使用晶体紫色染色量化生物膜抑制.
- 抗生素强化和排泄抑制通过MIC减少试验和乙基积累试验分别进行了评估.
主要成果:
- 提奥里达 (TZ) 有效地降低了生物膜的形成,并增强了针对*K. pneumoniae*在pH范围内的西普罗夫洛克萨 (CIP) 活性.
- 素 (Fx) 和素 (Sr) 显示出pH依赖的抗生物膜活性,Fx在性pH下对P.mirabilis特别有效.
- PAβN,CCCP和V9302显示出显著的抗生物膜和/或排泄抑制作用,通常具有pH依赖活性,并在耐药菌株中增强了CIP活性.
结论:
- 重用药物和EPI显示出作为治疗尿路感染的生物膜抑制剂和抗生素辅助剂的显著潜力.
- 这些药物的疗效可以受到pH值的影响,这表明了量身定制的治疗方法.
- 这些发现支持探索重新用途的药物和EPI作为对抗多药耐药性尿病原体的新战略.
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