Rezafungin 、Anidulafungin、Caspofungin 和 Micafungin 对中性粒细胞减少小鼠血流感染模型中四个念珠菌支系的体内疗效

IF 4.2 2区 生物学 Q2 MICROBIOLOGY Journal of Fungi Pub Date : 2024-08-29 DOI:10.3390/jof10090617
Dávid Balázsi, Zoltán Tóth, Jeffrey B. Locke, Andrew M. Borman, Lajos Forgács, Noémi Balla, Fruzsina Kovács, Renátó Kovács, Chiaki Amano, Tugba Ilay Baran, László Majoros
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In the lethality experiment and fungal tissue burden experiment (kidney, heart, and brain), cyclophosphamide-treated BALB/c male mice were intravenously infected (107 and 8 × 106 colony-forming units [CFU]/mouse, respectively). A 20 mg/kg dose of rezafungin was administered on days 1, 3, and 6. Alternatively, beginning 24 h post-infection, mice received 3 mg/kg of caspofungin, 5 mg/kg of micafungin, or 5 mg/kg of anidulafungin once daily for 6 days. Results: Regardless of isolate and clade, all echinocandin regimens improved survival after 21 days (p = 0.0041 to p < 0.0001). All echinocandins frequently produced >3-log mean CFU/g decreases in the fungal kidney and heart burdens, although some of these decreases were not statistically significant. Rezafungin, regardless of clade, produced 3–5 and 2–4 log CFU/g decreases in the kidney and heart burdens, respectively. Echinocandins did not inhibit fungal growth in the brain. Histopathological examination performed on day 7 showed no fungal cells in the heart and kidneys of rezafungin-treated mice and to a lesser extent, caspofungin-treated mice, regardless of the clinical isolate. All echinocandin-treated mice showed medium and/or large foci of fungal cells in their cerebrum or cerebellum. Conclusions: Regardless of the C. auris clade, rezafungin activity in vivo was comparable to or improved over that of the three previously approved echinocandins.","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In Vivo Efficacy of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in a Neutropenic Mouse Bloodstream Infection Model\",\"authors\":\"Dávid Balázsi, Zoltán Tóth, Jeffrey B. Locke, Andrew M. 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引用次数: 0

摘要

目标:雷沙芬净是十多年来首个获准用于治疗念珠菌血症和侵袭性念珠菌病的新药。然而,有关雷沙芬净和其他三种已获批准的棘白菌素对不同念珠菌支系的体内疗效的数据却很少。研究方法本研究涉及代表 4 个念珠菌支系的 10 个分离株:南亚(n = 2)、东亚(n = 2)、南非(n = 2)和南美(n = 4,包括 2 个环境分离株)。在致死实验和真菌组织负荷实验(肾脏、心脏和大脑)中,经环磷酰胺处理的 BALB/c 雄性小鼠被静脉注射感染(分别为 107 和 8 × 106 菌落总数形成单位 [CFU]/只小鼠)。第 1、3 和 6 天分别注射 20 mg/kg 剂量的雷扎芬净。另外,从感染后 24 小时开始,小鼠每天一次接受 3 毫克/千克的卡泊芬净、5 毫克/千克的米卡芬净或 5 毫克/千克的阿尼芬净,共持续 6 天。结果显示无论分离株和支系如何,所有棘白菌素方案都能提高 21 天后的存活率(p = 0.0041 至 p < 0.0001)。所有棘白菌素类药物都能使真菌肾脏和心脏负担的平均 CFU/g 下降 3 个对数值以上,但其中一些下降并无统计学意义。雷扎芬净(Rezafungin),不论是哪一支系,都能使肾脏和心脏负担分别减少 3-5 和 2-4 log CFU/g。棘白菌素不能抑制真菌在大脑中的生长。第 7 天进行的组织病理学检查显示,无论临床分离物是什么,雷扎芬净处理的小鼠心脏和肾脏中都没有真菌细胞,卡泊芬净处理的小鼠也没有。所有接受过棘白菌素治疗的小鼠的大脑或小脑中都出现了中型和/或大型真菌细胞灶。结论不论是哪种栗色葡萄球菌支系,雷沙芬净在体内的活性都与之前批准的三种棘白菌素相当,甚至更强。
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In Vivo Efficacy of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in a Neutropenic Mouse Bloodstream Infection Model
Objectives: Rezafungin is the first new drug approved to treat candidaemia and invasive candidiasis in more than 10 years. However, data are scant on the in vivo efficacy of rezafungin and the other three approved echinocandins against different Candida auris clades. Methods: This study involved 10 isolates representing 4 C. auris clades: South Asian (n = 2), East Asian (n = 2), South African (n = 2), and South American (n = 4, including 2 environmental isolates). In the lethality experiment and fungal tissue burden experiment (kidney, heart, and brain), cyclophosphamide-treated BALB/c male mice were intravenously infected (107 and 8 × 106 colony-forming units [CFU]/mouse, respectively). A 20 mg/kg dose of rezafungin was administered on days 1, 3, and 6. Alternatively, beginning 24 h post-infection, mice received 3 mg/kg of caspofungin, 5 mg/kg of micafungin, or 5 mg/kg of anidulafungin once daily for 6 days. Results: Regardless of isolate and clade, all echinocandin regimens improved survival after 21 days (p = 0.0041 to p < 0.0001). All echinocandins frequently produced >3-log mean CFU/g decreases in the fungal kidney and heart burdens, although some of these decreases were not statistically significant. Rezafungin, regardless of clade, produced 3–5 and 2–4 log CFU/g decreases in the kidney and heart burdens, respectively. Echinocandins did not inhibit fungal growth in the brain. Histopathological examination performed on day 7 showed no fungal cells in the heart and kidneys of rezafungin-treated mice and to a lesser extent, caspofungin-treated mice, regardless of the clinical isolate. All echinocandin-treated mice showed medium and/or large foci of fungal cells in their cerebrum or cerebellum. Conclusions: Regardless of the C. auris clade, rezafungin activity in vivo was comparable to or improved over that of the three previously approved echinocandins.
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来源期刊
Journal of Fungi
Journal of Fungi Medicine-Microbiology (medical)
CiteScore
6.70
自引率
14.90%
发文量
1151
审稿时长
11 weeks
期刊介绍: Journal of Fungi (ISSN 2309-608X) is an international, peer-reviewed scientific open access journal that provides an advanced forum for studies related to pathogenic fungi, fungal biology, and all other aspects of fungal research. The journal publishes reviews, regular research papers, and communications in quarterly issues. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on paper length. Full experimental details must be provided so that the results can be reproduced.
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