Evaluation of the Activity of Triazoles Against Non- fumigatus Aspergillus and Cryptic Aspergillus Species Causing Invasive Infections Tested in the SENTRY Program - PubMed (original) (raw)

Evaluation of the Activity of Triazoles Against Non- fumigatus Aspergillus and Cryptic Aspergillus Species Causing Invasive Infections Tested in the SENTRY Program

Michael A Pfaller et al. Open Forum Infect Dis. 2024.

Abstract

The activity of isavuconazole and other triazoles against non-fumigatus (non-AFM) Aspergillus causing invasive aspergillosis was evaluated. A total of 390 non-AFM isolates were collected (1/patient) in 2017-2021 from 41 hospitals. Isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and/or internal spacer region/β-tubulin sequencing and tested by Clinical and Laboratory Standards Institute (CLSI) broth microdilution. CLSI epidemiological cutoff values were applied, where available. Isavuconazole showed activity against Aspergillus sections Flavi (n = 122; minimum inhibitory concentration [MIC]50/90, 0.5/1 mg/L), Terrei (n = 57; MIC50/90, 0.5/0.5 mg/L), Nidulantes (n = 34; MIC50/90, 0.12/0.25 mg/L), Versicolores (n = 7; MIC50, 1 mg/L), and Circumdati (n = 2; MIC range, 0.12-2 mg/L). Similar activity was displayed by other triazoles against those Aspergillus sections. Most of the isolates from Aspergillus sections Fumigati (n = 9), Nigri (n = 146), and Usti (n = 12) exhibited elevated MIC values to isavuconazole (MIC50/90, 2/-, 2/4, and 2/8 mg/L), voriconazole (MIC50/90, 2/-, 1/2, and 4/8 mg/L), itraconazole (MIC50/90, 2/-, 2/4, and 8/>8 mg/L), and posaconazole (MIC50/90, 0.5/-, 0.5/1, and >8/>8 mg/L), respectively. Isavuconazole was active (MIC values, ≤1 mg/L) against Aspergillus parasiticus, Aspergillus tamarii, Aspergillus nomius, Aspergillus nidulans, Aspergillus unguis, Aspergillus terreus, Aspergillus alabamensis, and Aspergillus hortai, while isavuconazole MIC values between 2 and 8 mg/L were observed against cryptic isolates from Aspergillus section Fumigati. Isavuconazole inhibited 96.1% of Aspergillus niger and 80.0% of Aspergillus tubingensis at ≤4 mg/L, the CLSI wild-type cutoff value for A niger. Voriconazole, itraconazole, and posaconazole showed similar activity to isavuconazole against most cryptic species. Isavuconazole exhibited potent in vitro activity against non-AFM; however, the activity of triazoles varies among and within cryptic species.

Keywords: Aspergillus non-fumigatus; antifungal; cryptic species; invasive aspergillosis; triazole resistance.

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

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Conflict of interest statement

Potential conflicts of interest. JMI Laboratories was contracted to perform services in 2023 for AbbVie, Inc, Adamed Pharma S.A., AimMax Therapeutics, Allecra Therapeutics, Amicrobe, Inc, AN2 Therapeutics, Inc, Apnimed, Astellas Pharma, Inc, Basilea Pharmaceutica AG, Baxis Pharmaceuticals, Inc, Beckman Coulter, Inc, bioMérieux, Biosergen AB, Blacksmith Medicines, Bugworks, Carnegie Mellon University, Center for Discovery and Innovation, Cerba Research NV, Cidara Therapeutics, Cipla USA Inc, ContraFect Corporation, CorMedix Inc, Crestone, Inc, Discoveric Bio Beta Ltd, Dr. Falk Pharma GmbH, Entasis Therapeutics, Evopoint Biosciences, Fedora Pharmaceuticals, Forge Therapeutics, GARDP Foundation, Genentech, Gilead Sciences, Inc, GlaxoSmithKline plc, Harvard University, Institute for Clinical Pharmacodynamics, Iterum Therapeutics plc, Janssen Biopharma, Johnson & Johnson, Kbio, Inc, Lakewood-Amedex Inc, Locus Biosciences, Inc, McGill University, Medpace, Inc, Meiji Seika Pharma, Melinta Therapeutics, Menarini Group, Merck & Co, MetCura Pharmaceuticals, Inc, MicuRx Pharmaceutical Inc, Mundipharma International Ltd., Nabriva Therapeutics, National Cancer Institute, National Institutes of Health, NovoBiotic Pharmaceuticals, LLC, Ohio State University, Omnix Medical Ltd, Paratek Pharmaceuticals, Pfizer, Inc, PPD Global Central Labs, LLC, Pulmocide Ltd, Qpex Biopharma, Inc, Revagenix, Inc, Roche Holding AG, Scynexis, Inc, Seed Health, SeLux Diagnostics, Shionogi & Co, Ltd, Spero Therapeutics, Sumitovant Biopharma, Inc, Swedish National Reference Laboratory, TenNor Therapeutics, ThermoFisher Scientific, US Food and Drug Administration, University of Wisconsin, VenatoRx Pharmaceuticals, Wockhardt, and Zoetis, Inc. The authors report no individual conflicts of interest.

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