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在日本,体外和体内实验评估呋喃妥因对大肠杆菌临床分离株的抗菌活性,以及利用小鼠尿路感染模型评价呋喃妥因耐药株的生物学代价。

In vitro and in vivo antibacterial activity of nitrofurantoin against clinical isolates of E. coli in Japan and evaluation of biological cost of nitrofurantoin resistant strains using a mouse urinary tract infection model.

机构信息

Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan; Bio Science & Engineering Research Laboratories Research & Development Management Headquarters, FUJIFILM Corporation, 4-1, Shimookui 2-chome, Toyama, 930-8508, Japan.

Bio Science & Engineering Research Laboratories Research & Development Management Headquarters, FUJIFILM Corporation, 577 Ushijima, Kaisei-Machi, Ashigarakami-Gun, Kanagawa, 258-8577, Japan.

出版信息

J Infect Chemother. 2021 Feb;27(2):250-255. doi: 10.1016/j.jiac.2020.09.026. Epub 2020 Oct 12.

Abstract

INTRODUCTION

Nitrofurantoin is a well-established antibiotic, and is an important first-line oral treatment for uncomplicated urinary tract infections. However, little information is available with respect to its antibacterial activity in Japan, in vivo efficacy, or the in vivo biological cost of resistant strains.

METHODS

We compared the susceptibility of six representative antibacterial agents-nitrofurantoin, sulfamethoxazole/trimethoprim, fosfomycin, mecillinam, ciprofloxacin, and cefdinir-against E. coli clinically isolated in Japan during 2017. We evaluated the in vivo efficacy of nitrofurantoin using a model of mouse urinary tract infection caused by ciprofloxacin resistant E. coli. We obtained nitrofurantoin resistant isolates through tests generating spontaneous mutations, and assessed the in vivo fitness of nitrofurantoin resistant isolates.

RESULTS

The MIC of nitrofurantoin was 16 μg/mL, and was the lowest among the drugs tested. It was found that, in the mouse urinary tract infection model, 30 mg/kg and 100 mg/kg of nitrofurantoin reduced the count of viable bacterial cells in the kidney, while 100 mg/kg of ciprofloxacin did not. All spontaneous bacterial mutants resistant to nitrofurantoin had deletions in the nfsA gene, and we found that the resistant strain had lower growth in the mouse urinary tract infection model than in the parent strain.

CONCLUSIONS

We demonstrated promising in vitro and in vivo activity of nitrofurantoin against E. coli clinical isolates in Japan, and lower in vivo fitness of the resistant strain of nitrofurantoin.

摘要

简介

呋喃妥因是一种成熟的抗生素,是治疗单纯性尿路感染的重要一线口服药物。然而,关于其在日本的抗菌活性、体内疗效或耐药菌株的体内生物代价的信息很少。

方法

我们比较了六种代表性的抗菌药物-呋喃妥因、磺胺甲恶唑/甲氧苄啶、磷霉素、美西林、环丙沙星和头孢地尼-对 2017 年日本临床分离的大肠杆菌的敏感性。我们使用由环丙沙星耐药大肠杆菌引起的小鼠尿路感染模型来评估呋喃妥因的体内疗效。我们通过产生自发突变的试验获得了对呋喃妥因耐药的分离株,并评估了其体内适应性。

结果

呋喃妥因的 MIC 为 16μg/ml,是所有测试药物中最低的。结果表明,在小鼠尿路感染模型中,30mg/kg 和 100mg/kg 的呋喃妥因可降低肾脏中活菌细胞的数量,而 100mg/kg 的环丙沙星则不能。所有对呋喃妥因耐药的自发突变细菌都在 nfsA 基因缺失,我们发现耐药菌株在小鼠尿路感染模型中的生长速度低于亲本菌株。

结论

我们证明了呋喃妥因对日本临床分离的大肠杆菌具有良好的体外和体内活性,并且其耐药菌株的体内适应性较低。

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