PDF(Pubmed)
Abstract：
Invasive fungal infections have recently been recognized by the WHO as a major health, epidemiological, and economic issue. Their high mortality rates and the emergence of drug resistance have driven the development of new molecules, including olorofim, an antifungal belonging to a new family of compounds, the orotomides. A review was conducted on the PubMed database and the ClinicalTrials.gov website to summarize the microbiological profile of olorofim and its role in the treatment of filamentous fungal infections. Twenty-four articles were included from the search and divided into two groups: an \"in vitro\" group focusing on minimum inhibitory concentration (MIC) results for various fungi and an \"in vivo\" group evaluating the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and tolerability of olorofim in animal models of fungal infection and in humans. Olorofim demonstrated in vitro and in vivo activity against numerous filamentous fungi, including azole-resistant Aspergillus fumigatus, various dermatophytes, and endemic and dimorphic fungi. in vitro results showed higher MICs for certain Fusarium species and dematiaceous fungi Alternaria alternata and Exophiala dermatitidis; further in vivo studies are needed. Published PK-PD data in humans are limited. The results of the ongoing phase III clinical trial are eagerly awaited to evaluate olorofim\'s clinical impact.
摘要：
侵袭性真菌感染最近被世界卫生组织认为是一个主要的健康，流行病学,和经济问题。它们的高死亡率和耐药性的出现推动了新分子的开发,包括奥洛菲姆,一种属于新化合物家族的抗真菌药物，orotomides.对PubMed数据库和ClinicalTrials.gov网站进行了综述，以总结olorofim的微生物学特征及其在丝状真菌感染治疗中的作用。从搜索中纳入了24篇文章，分为两组：“体外”组专注于各种真菌的最低抑制浓度（MIC）结果，“体内”组评估药代动力学（PK），药效学（PD），功效,在真菌感染的动物模型和人类中，olorofim的耐受性。Olorofim在体外和体内表现出对许多丝状真菌的活性，包括耐唑的烟曲霉,各种皮肤癣菌，以及地方性和双态真菌。体外结果表明，某些镰刀菌物种和致命性真菌Alternariaalternata和Exophialadermatitidis的MIC较高；需要进一步的体内研究。在人类中公开的PK-PD数据是有限的。正在进行的III期临床试验的结果正在热切期待，以评估olorofim的临床影响。
