Does Cryptococcus neoformans infection alter antifungal distribution: an animal model exploring pharmacokinetic changes.

IF 2.5 4区生物学 Q3 MICROBIOLOGY

Future microbiology Pub Date : 2025-04-01 Epub Date: 2025-04-03 DOI:10.1080/17460913.2025.2484956

Izabel Almeida Alves, Keli Jaqueline Staudt, Bruna Gaelzer Silva Torres, Calinca Elioterio Oliveira, Ryan Lago Araujo Rieper, Layza Kowalski, Bibiana Verlindo de Araújo

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Abstract

Aim: Assessing the disseminated meningitis caused by Cryptoccocus neoformans in Wistar rats and its impact on antifungal distribution by microdialysis (µD).

Materials & methods: The yeast presence was investigated in different tissues by histological and microbiological assays, and biochemical parameters such as urea, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatinine, creatine kinase (CK), creatinine, albumin level, leukocyte counts, and brain vascular permeability (Evans blue test) were evaluated in healthy and infected groups. Levels of fluconazole reached in the animal's brain were determined by µD.

Results: Differences in albumin, urea, GPT, and CK between healthy and infected animals were observed in the levels of Evans blue as well as in the brain (0.51 vs 1.50 µg/g_brain). The drugs' distribution in the brain of infected animals was higher than that in the brain of healthy ones (ft = 1.37 vs ft = 0.54).

Conclusion: The model validated presents characteristics similar to those observed in patients and can be applied to pharmacokinetic investigations.

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新型隐球菌感染是否会改变抗真菌药的分布：一个探索药代动力学变化的动物模型。

材料与方法：通过微透析（µD）评估隐球菌引起的Wistar大鼠播散性脑膜炎及其对抗真菌分布的影响：通过组织学和微生物学检测法研究不同组织中酵母菌的存在情况，并评估健康组和感染组的生化指标，如尿素、谷氨酸草酰乙酸转氨酶（GOT）、谷氨酸丙酮酸转氨酶（GPT）、肌酐、肌酸激酶（CK）、肌酐、白蛋白水平、白细胞计数和脑血管通透性（埃文斯蓝试验）。用 µD 测定动物脑内氟康唑的含量：结果：健康组和感染组动物的白蛋白、尿素、GPT 和肌酸激酶在埃文斯蓝和大脑中的水平存在差异（0.51 vs 1.50 µg/grain）。药物在感染动物大脑中的分布高于健康动物（ft = 1.37 vs ft = 0.54）：结论：所验证的模型具有与在患者身上观察到的相似特征，可用于药代动力学研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future microbiology 生物-微生物学

CiteScore

4.90

自引率

3.20%

发文量

134

审稿时长

6-12 weeks

期刊介绍： Future Microbiology delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this increasingly important and vast area of research.