Su Huilin, Zhu Min, Tsui Clement Kin-Ming, van der Lee Henrich, Tehupeiory-Kooreman Marlou, Zoll Jan, Engel Tobias, Li Li, Zhu Junhao, Lu Zihan, Zhang Qiangqiang, Verweij Paul E, Deng Shuwen
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Medical Microbiology and Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, The Netherlands.
Antimicrob Agents Chemother. 2023 May 1;65(5). doi: 10.1128/AAC.02546-20. Epub 2021 Mar 8.
Triazole resistance in is an increasing worldwide problem that causes major challenges in the management of aspergillosis. New antifungal drugs are needed with novel targets, that are effective in triazole-resistant infection. In this study, we retrospectively evaluated potency of the novel drug olorofim compared to contemporary antifungal agents against 111 clinical isolates collected from Huashan Hospital, Shanghai, China, using EUCAST methodology, and reviewed the literature on triazole resistant published between 1966 and 2020 in China. Olorofim was active in vitro against all tested isolates with MIC of 0.031mg/L (range 0.008-0.062 mg/L). For 4 triazole-resistant (TRAF) isolates, the olorofim MIC ranged between 0.016-0.062mg/L. The reported rates of TRAF in China is 2.5% - 5.56% for clinical isolates, and 0-1.4% for environmental isolates.TR/L98H/S297T/F495I is the predominant resistance mechanism, followed by TR/L98H. Non TR-mediated TRAF isolates, mostly harboring a cyp51A single point mutation, showed greater genetic diversity than TR-mediated resistant isolates. Resistance due toTR/L98H and TR/L98H/S297T/F495I mutations among TRAF isolates might have evolved from separate local isolates in China. Continuous isolation of TRAF in China underscores the need for systematic resistance surveillance as well as the need for novel drug targets such as olorofim.
曲霉菌中的三唑耐药性是一个日益严重的全球性问题，给曲霉病的治疗带来了重大挑战。需要有针对新靶点的新型抗真菌药物，以有效治疗三唑耐药感染。在本研究中，我们采用EUCAST方法，回顾性评估了新型药物奥洛罗芬与当代抗真菌药物相比，对从中国上海华山医院收集的111株临床曲霉菌分离株的抗菌效力，并回顾了1966年至2020年期间中国发表的关于三唑耐药曲霉菌的文献。奥洛罗芬在体外对所有测试的曲霉菌分离株均有活性，MIC为0.031mg/L（范围为0.008 - 0.062mg/L）。对于4株三唑耐药曲霉菌（TRAF）分离株，奥洛罗芬的MIC范围在0.016 - 0.062mg/L之间。中国临床分离株中TRAF的报告发生率为2.5% - 5.56%，环境分离株为0 - 1.4%。TR/L98H/S297T/F495I是主要的耐药机制，其次是TR/L98H。非TR介导的TRAF分离株大多携带cyp51A单点突变，其遗传多样性高于TR介导的耐药分离株。TRAF分离株中由TR/L98H和TR/L98H/S297T/F495I突变引起的耐药可能源自中国不同的本地分离株。中国持续出现TRAF分离株凸显了系统耐药监测的必要性以及对新型药物靶点（如奥洛罗芬）的需求。
