In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 65, No. 5 ( 2021-04-19)
Abstract:
Triazole resistance in Aspergillus 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 the 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 we reviewed the literature on triazole-resistant A. fumigatus (TRAF) published between 1966 and 2020 in China. Olorofim was active in vitro against all tested A. fumigatus isolates, with a MIC 90 of 0.031 mg/liter (range, 0.008 to 0.062 mg/liter). For 4 triazole-resistant A. fumigatus isolates, the olorofim MIC ranged between 0.016 and 0.062 mg/liter. The reported rates of TRAF in China are 2.5 to 5.56% for clinical isolates and 0 to 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 to TR 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.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.02546-20
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2021
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
Permalink