Most clinical isolates identified as triazole-resistant Aspergillus niger by traditional laboratory microscopy and culture-based methods were revealed by DNA sequencing to be A tubingensis, in a cross-sectional study of clinical cultures collected in Southern California.1
A substantial proportion (15.1%) of the putative A niger isolates collected grew at the epidemiological cut-off for itraconazole, and 73.8% of these were determined by genomic sequencing and phylogenetic analysis to be A tubingensis.
"Our study revealed that nearly three-quarters of clinical isolates initially identified as A niger based on morphologic findings were in fact A tubingensis on molecular characterization, highlighting this cryptic species as an underrecognized cause of aspergillosis in Southern California," reported Yashan Wang, MHS, PhD, Department of Environmental and Occupational Health, Antibiotic Resistance Action Center, The George Washington University, Washington, DC, and colleagues.
In invited commentary,2 Sarah Ahmed, PhD, Department of Microbiology, Kuwait University, Kuwait, and David Denning, FRCP, FRCPath, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK, remark on the advances in medical mycology and precision diagnostics bringing attention to the A niger complex and A tubingensis in particular.
"Too often A niger is regarded as only a contaminant or colonizing organism, yet it can be deadly," observed Ahmed and Denning."These new data demand closer attention be paid in clinical laboratories to all A niger isolations, and routine antifungal susceptibility testing is probably called for, assuming antifungal therapy is appropriate."
What You Need to Know
Nearly three-quarters of isolates initially labeled as Aspergillus niger were actually A tubingensis upon genomic sequencing, revealing a major diagnostic gap in routine microscopy-based identification.
Among confirmed A tubingensis isolates, 71% had MICs above epidemiologic cutoffs—especially for posaconazole and itraconazole—highlighting clinically relevant antifungal resistance patterns.
Experts urge closer attention to A niger complex isolates and routine susceptibility testing, as triazole-resistant A tubingensis challenges treatment options and underscores the importance of antifungal stewardship and precision mycology.
The investigators collected over 2,000 clinical Aspergillus cultures from September 1, 2019 to June 30, 2023 at the Kaiser Permanente Southern California, a regional health system. Of those, 1,835 were successfully cultured for Aspergillus, and 1,505 of these were screened for triazole resistance (using the Centers for Disease Control and Prevention resistance screening method). In addition, patient care records were reviewed to identify previous antifungal treatment in the patients with triazole-resistant Aspergillus infection.
Among all cultures, the most frequently found species identified by clinical laboratory were A niger (n=1,002), A fumigatus (n=996) and A terreus (n=316).The investigators noted that species varied by specimen source, with A fumigatus and A niger comprising 80.1% and 44.7% of cultures from respiratory samples, respectively.Phylogenetic analysis revealed that A tubigensis was the most common species among A niger complex clinical isolates.
Minimum inhibitory concentrations (MICs) among the confirmed A tubingensis isolates were determined for itraconazole, voriconazole, posaconazole and isavuconazole. Among the 59 A tubigensis isolates, 42 (71.2%) had MICs above the A niger epidemiological cut-offs.The investigators reported that elevated MICs were most frequent for posaconazole (n=32), followed by itraconazole (n=25), voriconazole (n=11) and isavuconazole (n=4).They noted, further, that 17 isolates showed elevated MICs to both itraconazole and posaconazole, and one had elevated MICs to all 4 antifungal agents.
Wang and colleagues emphasize that triazole antifungals are essential for treating Aspergillus infections, and the emergence of resistant strains are problematic. Although their in-vitro data showed that itraconazole and posaconazole have limited clinical utility against A tubingensis, they found fewer instances of resistance to voriconazole and isavuconazole and suggest, with a note of caution, that current treatment guidelines remain valid.
"The limited treatment options underscore the importance of antifungal stewardship across clinical and environmental domains," Wang and colleagues advise.
References
1. Wang Y, Aziz M, Bush K, et al. Triazole resistance and misidentification of Aspergillus tubingensis in Southern California. JAMA Netw Open. 2025;8(12):e2543630. doi:10.110/jamanetworkopen.2025.43630.
2. Ahmed SA, Denning DW. Black Aspergillus tubingensis in California. JAMA Netw Open. 2025;8(12):e2543627.doi:10.1001/jamanetworkoen.2025.43627
