Kirchhoff Lisa, Dittmer Silke, Buer Jan, Rath Peter-Michael, Steinmann Joerg
Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; Institute for Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum Nuernberg, Paracelsus Medical University, Prof.-Ernst-Nathan-Str. 1, 90419 Nuremberg, Germany.
Int J Antimicrob Agents. 2020 Sep;56(3):106105. doi: 10.1016/j.ijantimicag.2020.106105. Epub 2020 Jul 25.
In recent decades, invasive infections caused by fungal pathogens have been reported with increasing frequency. Concurrently, the rates of detected resistance mechanisms against commonly used antifungal agents in fungi are increasing. The need for novel antifungal drugs is thus imminent. In this study, the novel drug olorofim (F901318) was tested for its antifungal activity against the human fungal pathogens Lomentospora prolificans (n = 20), Scedosporium aurantiacum (n = 2), Scedosporium apiospermum (n = 6), Rasamsonia argillacea species complex (n = 23), Exophiala dermatitidis (n = 10) and azole-resistant Aspergillus fumigatus (ARAF) (n = 25) in an in vitro broth microdilution assay according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations. Whilst olorofim was ascertained to be effective against R. argillacea species complex [minimum inhibitory concentrations (MICs) of ≤0.008 mg/L], Scedosporium spp. (MICs of 0.032-0.5 mg/L), L. prolificans (MICs of 0.032-0.5 mg/L) and ARAF (MICs of ≤0.008-0.032 mg/L), the drug had an MIC of >4 mg/L against E. dermatitidis. These data demonstrate the antifungal activity of olorofim against a broad range of filamentous fungal pathogens.
近几十年来,由真菌病原体引起的侵袭性感染报告频率不断增加。与此同时,真菌中针对常用抗真菌药物的耐药机制检出率也在上升。因此,新型抗真菌药物的需求迫在眉睫。在本研究中,根据欧洲抗菌药物敏感性试验委员会(EUCAST)的建议,采用体外肉汤微量稀释法,对新型药物奥拉罗芬(F901318)针对人类真菌病原体多育镰孢菌(n = 20)、桔青霉(n = 2)、伪阿利什霉(n = 6)、泥生拉氏菌复合种(n = 23)、皮炎外瓶霉(n = 10)和耐唑类烟曲霉(ARAF)(n = 25)的抗真菌活性进行了测试。虽然确定奥拉罗芬对泥生拉氏菌复合种有效[最低抑菌浓度(MIC)≤0.008 mg/L]、对青霉属(MIC为0.032 - 0.5 mg/L)、多育镰孢菌(MIC为0.032 - 0.5 mg/L)和耐唑类烟曲霉(MIC为≤0.008 - 0.032 mg/L)有效,但该药物对皮炎外瓶霉的MIC >4 mg/L。这些数据证明了奥拉罗芬对多种丝状真菌病原体具有抗真菌活性。