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Triazole Resistance and Misidentification of Aspergillus tubingensis in Southern California
Journal article   Open access   Peer reviewed

Triazole Resistance and Misidentification of Aspergillus tubingensis in Southern California

Yashan Wang, Maliha Aziz, Kaeley Bush, Gregg S Davis, Jeffrey T Foster, Søren Hallstrøm, Amber Jones, Paul S Keim, Reed Leventis, Cindy M Liu, …
JAMA network open, Vol.8(12), e2543630
2025
DOI: https://doi.org/10.1001/jamanetworkopen.2025.43630
PMID: 41343218
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Published1.04 MBDownloadView
CC BY V4.0,  Open Access

Abstract

Adult Antifungal Agents - pharmacology Antifungal Agents - therapeutic use Aspergillosis - diagnosis Aspergillosis - drug therapy Aspergillosis - epidemiology Aspergillosis - microbiology Aspergillus - classification Aspergillus - drug effects Aspergillus - genetics Aspergillus - isolation & purification California - epidemiology Cross-Sectional Studies Drug Resistance, Fungal - genetics Female Humans Male Microbial Sensitivity Tests Middle Aged Triazoles - pharmacology Triazoles - therapeutic use
Accurate species identification and antifungal susceptibility testing are essential for effective aspergillosis treatment. However, non-Aspergillus fumigatus species, such as Aspergillus tubingensis, are often misidentified and understudied, potentially compromising proper prognosis and treatment. To examine the species and prevalence of triazole resistance among clinical Aspergillus isolates in Southern California. This cross-sectional study collected clinical Aspergillus cultures from September 1, 2019, to June 30, 2023, at Kaiser Permanente Southern California, an integrated health system serving a diverse regional population. Triazole susceptibility testing and whole genome sequencing were performed on selected isolates. A total of 2421 consecutive Aspergillus cultures were included. Eighty putative Aspergillus niger isolates were selected for sequencing, including 44 with positive growth in the presence of at least one clinically relevant triazole. The primary outcome was the genome-based species identification of A tubingensis. The secondary outcome was triazole susceptibility above the A niger epidemiological cut-off values. The hypothesis that A tubingensis is a prevalent, underrecognized, triazole-resistant pathogen was developed during data collection. Of 2421 cultures, 1835 were successfully cultured for Aspergillus. After purification and deduplication, 1505 isolates were screened for triazole resistance. A substantial fraction of putative A niger isolates grew at the A niger epidemiological cut-off for itraconazole (110 of 664 [15.1%]). DNA sequencing revealed that 59 of 80 putative A niger isolates (73.8%) were actually A tubingensis. Elevated triazole minimum inhibitory concentrations were not strongly associated with any known cyp51 mutations among the A tubingensis isolates. In this cross-sectional study of Aspergillus isolates from Kaiser Permanente Southern California, A tubingensis was a prevalent but underrecognized cause of aspergillosis in Southern California. Its frequent misidentification, association with invasive infections, and triazole resistance underscore the need for improved diagnostics and species-specific epidemiological investigations.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.148 Medical Mycology
1.148.94 Antifungal Strategies
Web Of Science research areas
Microbiology
ESI research areas
Clinical Medicine
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