Exposure to resistant fungi across working environments and time
Antifungal resistance has become an emerging health concern and resistant variants of previously susceptible species are increasingly reported. At present, little is known about occupational exposure to antifungal resistant fungi. The purpose of this study was to obtain knowledge about Danish workers' occupational exposure to airborne fungi resistant to first-line treatment drugs. A retrospective study was performed on a unique collection of personal exposure samples, obtained over a twenty-year period from Danish working environments in sectors including agriculture, animal handling, waste management, and healthcare. In total 692 samples were cultivated at 37 °C and fungal colonies were identified using MALDI-TOF MS and subsequently by sequencing of calmodulin and beta-tubulin to reveal potential cryptic species.  Infectious fungi (495 isolates from 23 species), were tested for resistance against Itraconazole, Voriconazole, Posaconazole, and Amphotericin B. Working environments were highly variable in the overall fungal exposure, and in addition, had vastly different species compositions. Resistance was found in 30 isolates of the species Aspergillus fumigatus (4 of 251 isolates), A. nidulans (2 of 13), A. niger complex (19 of 131), A. versicolor (3 of 18) and A. lentulus (2 of 2). Sequence analysis revealed several cryptic species within the A. niger complex including A. tubingensis, A. luchuensis, and A. phoenicis. Of the resistant A. fumigatus isolates, two contained the well described TR34/L98H mutation in the cyp51A gene and promoter region, while the remaining harbored silent mutations. Our results indicate that the working environment can be a contributing factor for exposure to resistant fungi with particularly high exposure observed for biofuel plant workers. Differences in the prevalence of resistance across working environments may be linked to the underlying species composition