Abstract
Introduction: The frequency in detection of azole-resistant Aspergillus fumigatus isolates has increased since 2010. In Portugal, the section Fumigati is one of the most frequent, and resistant strains to have been found in clinical and environmental contexts. Although several cryptic species within the Fumigati section show intrinsic resistance to azoles, one factor driving (acquired) resistance is selective pressure deriving from the extensive use of azoles. This is particularly problematic in occupational environments where high fungal loads are expected, and where there is an increased risk of human exposure and infection, with impact on treatment success and disease outcome. The mechanisms of resistance are diverse, but mainly associated with mutations in the cyp51A gene. Despite TR34/L98H being the most frequent mutation described, it has only been detected in clinical specimens in Portugal. Methods: We analyzed 99 A. fumigatus isolates from indoor environments (healthcare facilities, spas, one dairy and one waste sorting unit) collected from January 2018 to February 2019 in different regions of Portugal. Isolates were screened for resistance to itraconazole, voriconazole and posaconazole by culture, and resistance was confirmed by broth microdilution. Sequencing of the cyp51A gene and its promoter was performed to detect mutations associated with resistance. Results: Overall, 8.1% of isolates were able to grow in the presence of at least one azole, and 3% (isolated from the air in a dairy and from filtering respiratory protective devices in a waste sorting industry) were pan-azole-resistant, bearing the TR34/L98H mutation. Conclusion: For the first time in Portugal, we report environmental isolates bearing the TR34/L98H mutation, isolated from occupational environments. Environmental surveillance of the emergence of azole-resistant A. fumigatus sensu stricto strains is needed, to ensure proper and timely implementation of control policies that may have a positive impact on public and occupational health.
Highlights
The frequency in detection of azole-resistant Aspergillus fumigatus isolates has increased since 2010
The objective of this study was to assess the frequency of cryptic species belonging to Fumigati section and determine the frequency of azole resistance in A. fumigatus sensu stricto strains isolated from environmental samples
Our aim was to improve the knowledge of the Fumigati epidemiology in these environmental settings and to understand the molecular mechanisms involved in azole resistance in these isolates
Summary
The frequency in detection of azole-resistant Aspergillus fumigatus isolates has increased since 2010. Several cryptic species within the Fumigati section show intrinsic resistance to azoles, one factor driving (acquired) resistance is selective pressure deriving from the extensive use of azoles This is problematic in occupational environments where high fungal loads are expected, and where there is an increased risk of human exposure and infection, with impact on treatment success and disease outcome. The Fumigati section is one of the most prevalent Aspergillus sections, in the clinical context as well as in the environment, in Portugal [1,2,3] and elsewhere [4,5,6,7,8,9,10,11] They can be isolated from air, water, or soil, and can contaminate indoor environments. Infection in immunocompetent individuals is not frequent, exposure to largely contaminated environments as it happens in agriculture, in wood and food ( animal) industries, and in waste handling increases the risk of infection
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