梅罗,阿维巴克坦和金属β-乳糖酶抑制剂的三重组合优化了对不同β-乳糖酶生产者的抗菌覆盖
Zhuoren Ling1, Alistair James Macdonald Farley2, Aditya Lankapalli1
1Department of Biology & Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford OX1 3RE, UK.
Engineering (Beijing, China)
|March 20, 2025
概括
梅罗,MBL抑制剂 (InC58) 和SBL抑制剂 (avibactam) 的三重组合显示出对产生卡巴酶的细菌的广泛活性. 这一策略有效地打击抗菌素耐药性,但并非针对所有耐药菌株.
科学领域:
- 抗微生物耐药性 抗微生物耐药性
- 细菌遗传学 细菌遗传学
- 药物发现 药物发现
背景情况:
- 产生碳酶的细菌对全球健康构成重大威胁.
- 由于耐药性机制,现有的抗生素治疗越来越无效.
- 金属β-乳糖酶 (MBL) 和血清β-乳糖酶 (SBL) 是关键的卡巴酶.
研究的目的:
- 评估三重组合疗法对产生碳烯酶的细菌的广泛活性.
- 研究对这种新型组合的耐药性频率和机制.
- 评估这种三重组合作为对抗抗菌素耐药性的战略的潜力.
主要方法:
- 使用阿加稀释剂对三重组合 (美罗,InC58,阿维巴克坦) 的敏感性测试.
- 对美罗胺的耐药性 (FoR) 频率的研究加上InC58.8.
- 抗性突变体的测序,以识别遗传突变并评估交叉抗性和适应性.
主要成果:
- 三重组合表明对产生SBLs (OXA-48,KPC-2) 和MBLs (NDMs) 的菌株的扩展活性.
- 对产生VIM的*Pseudomonas aeruginosa*和产生OXA-23的*Acinetobacter baumannii*活动是有限的.
- 抵抗与*ompC*和*comR*的突变相关,突变者表现出适应性成本和交叉抵抗.
结论:
- 梅罗,InC58和阿维巴克坦的三重组合提供了比双重组合更广泛的活性范围.
- 这种方法代表了一种有前途的新策略,用于对抗β-乳糖酶介导的抗菌素耐药性.
- 需要进一步的研究,以克服特定具有挑战性的细菌菌株的耐药性.
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