Abstract

Background

MDR bacterial infections are currently a serious problem for clinicians worldwide. Klebsiella pneumoniae and Enterobacter spp., among Enterobacteriaceae, and Pseudomonas aeruginosa, are part of the group of ESCAPE pathogens or bacteria that ‘escape’ from common antibacterial treatments. The lack of effectiveness of the first common line of antibiotics has led to the search for new therapies based on older antibiotics, such as colistin.

Objectives

We searched for new enhancers of the action of colistin against MDR Gram-negative bacteria that can be easily applicable to clinical treatments.

Methods

Colistin MICs were determined alone and with the protonophores CCCP, sodium benzoate, sodium salicylate and aspirin using the broth microdilution method and FIC indexes were calculated to assess synergy between colistin and each chemical. Time–kill assays of colistin with and without protonophores were performed to determine the bactericidal action of combinations of colistin with protonophores. Likewise, the effect of sucrose, l-arginine and l-glutamic acid on the MICs of colistin alone and combined with each protonophore was assessed.

Results

It was found that sodium benzoate, sodium salicylate and aspirin, at concentrations allowed for human and animal use, partially or totally reversed resistance to colistin in P. aeruginosa and highly resistant enterobacterial strains. The mechanism of action could be related to their negative charge at a physiological pH along with their lipid-soluble character.

Conclusions

Sodium benzoate, sodium salicylate and aspirin are good enhancers to use in antibiotic therapies that include colistin.

中文翻译：

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阿司匹林，苯甲酸钠和水杨酸钠逆转肠杆菌科细菌和铜绿假单胞菌对大肠菌素的抗性

摘要

背景

对于全世界的临床医生来说，MDR细菌感染目前是一个严重的问题。肠杆菌科和铜绿假单胞菌中的肺炎克雷伯菌和肠杆菌属属于ESCAPE病原体或细菌类的一部分，它们从常规抗菌治疗中“逃脱”。第一类普通抗生素的有效性不足导致人们寻求基于旧抗生素（如粘菌素）的新疗法。

目标

我们寻找了大肠菌素针对MDR革兰氏阴性细菌的作用的新增强剂，它们可以轻松地应用于临床治疗。

方法

使用肉汤微量稀释法单独测定colistin MIC，并与质子载体CCCP，苯甲酸钠，水杨酸钠和阿司匹林一起测定，并计算FIC指数以评估大肠菌素与每种化学物质之间的协同作用。进行带有和不带有质子体的粘菌素的时间杀灭试验，以确定粘菌素与质子体组合的杀菌作用。同样，评估了蔗糖，1-精氨酸和1-谷氨酸对粘菌素单独和与每个质子体结合的MIC的影响。

结果

已发现，在允许用于人类和动物的浓度下，苯甲酸钠，水杨酸钠和阿司匹林可以部分或完全逆转铜绿假单胞菌和高度耐药的肠杆菌菌株对大肠菌素的耐药性。作用机理可能与其在生理pH下的负电荷及其脂溶性特征有关。

结论

苯甲酸钠，水杨酸钠和阿司匹林是用于包括大肠菌素在内的抗生素治疗的良好增强剂。