Potency of olorofim (F901318) compared to contemporary antifungal agents against clinical Aspergillus fumigatus isolates, and review of azole resistance phenotype and genotype epidemiology in China.

Autor: Su H; 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.; Department of Dermatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Zhu M; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China., Tsui CK; Department of Pathology, Sidra Medicine, Doha, Qatar.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-Qatar, Qatar.; Division of Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., van der Lee H; Department of Medical Microbiology and Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, The Netherlands., Tehupeiory-Kooreman M; Department of Medical Microbiology and Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, The Netherlands., Zoll J; Department of Medical Microbiology and Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, The Netherlands., Engel T; Department of Medical Microbiology and Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, The Netherlands., Li L; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China., Zhu J; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China., Lu Z; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China., Zhang Q; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China., Verweij PE; Department of Medical Microbiology and Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, The Netherlands Paul.Verweij@radboudumc.nl.; Center for Infectious Diseases Research, Diagnostics and Laboratory Surveillance, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands., Deng S; Department of Medical Microbiology, The People's Hospital of Suzhou New District, Suzhou, Jiangsu, China shuwen.deng@gmail.com.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2023 May 01; Vol. 65 (5). Date of Electronic Publication: 2021 Mar 08.
DOI: 10.1128/AAC.02546-20
Abstrakt: Triazole resistance in A. fumigatus 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 A. fumigatus isolates collected from Huashan Hospital, Shanghai, China, using EUCAST methodology, and reviewed the literature on triazole resistant A. fumigatus published between 1966 and 2020 in China. Olorofim was active in vitro against all tested A. fumigatus isolates with MIC 90 of 0.031mg/L (range 0.008-0.062 mg/L). For 4 triazole-resistant A. fumigatus (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 34 /L98H/S297T/F495I is the predominant resistance mechanism, followed by TR 34 /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 34 /L98H and TR 34 /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.
(Copyright © 2021 Su et al.)
Databáze: MEDLINE
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