Triazole Resistance and Misidentification of Aspergillus tubingensis in Southern California

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.