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生长介质在检测格拉姆阴性细菌中药物相互作用的关键作用,这种细菌模拟着体内反应

Kathleen P Davis¹, Yoelkys Morales^1,2, Rachel J Ende¹

¹Department of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance Boston, Boston, Massachusetts, USA.

|February 16, 2024

概括

抗生素药物相互作用在细菌物种和生长条件之间有很大差异. 最少的生长介质,而不是丰富的介质,准确地预测了抗生素组合在某些病原体的肺部感染中如何表现.

科学领域:

微生物学微生物学
传染性疾病传染性疾病
药理学药理学是指药理学的学科.

背景情况:

耐多药性 (MDR) 细菌感染构成了重大的临床挑战,推动了对抗生素组合等有效治疗策略的需求.
SARS-CoV-2 流行病加剧了耐药性感染的增加,增加了确定可靠方法来选择有效的抗生素组合的重要性,特别是对于阴性细菌.

研究的目的:

研究不同生长介质 (富含,模仿尿液和最小) 如何影响对抗 Gram 阴性 ESKAPE 病原体 (Acinetobacter baumannii,Klebsiella pneumoniae,Pseudomonas aeruginosa) 的对抗生素相互作用.
确定哪些体外生长条件在相关的感染模型 (小鼠肺) 中最好预测体内抗生素相互作用.

主要方法:

在三种不同的介质中对抗生素相互作用的系统测试:穆勒-亨顿 (CAMHB),尿液模拟介质 (UMM) 和最小介质 (M9Glu).
对三种格拉姆阴性病原体的相互作用的评估:Acinetobacter baumannii (Ab),Klebsiella pneumoniae (Kp) 和Pseudomonas aeruginosa (Pa). 这三种病原体的相互作用包括:Acinetobacter baumannii (Ab),Klebsiella pneumoniae (Kp) 和 Pseudomonas aeruginosa (Pa).
通过将其与Kp.的小鼠肺部感染模型中抗生素组合的体内结果进行比较来验证体外发现.

主要成果:

在同一介质内的细菌物种之间,抗生素相互作用概况在不同细菌物种之间有显著的差异.
在所有测试的介质中,Pseudomonas aeruginosa表现出一致的药物相互作用模式.
在丰富的 (CAMHB) 和最小的 (M9Glu) 介质中,Acinetobacter baumannii表现出类似的相互作用,而Klebsiella pneumoniae显示出不同介质之间的相互作用的相关性较差.
在最小介质 (M9Glu) 的体外抗生素相互作用在Kp的小鼠肺部感染模型中成功预测了体内结果,而丰富介质和UMM则没有.

结论:

抗生素药物相互作用高度依赖于生长介质和细菌物种.
最小生长介质提供了一个更准确的体外模型,用于预测体内抗生素有效性和某些格兰氏阴性病原体的相互作用,而不是标准的丰富介质.
这些发现强调了选择适当的体外模型的重要性,这些模型模仿生理条件,以指导开发有效的抗生素联合治疗药物耐药性感染的方法.

关键词:

这是Acinetobacter.克莱布西埃拉菌 (Klebsiella) 是一种植物.伪omonas空气菌伪omonas空气菌抗生素耐药性抗生素耐药性组合疗法治疗组合治疗.

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