Temporal links between ambient air pollutants and antifungal resistance dynamics in Candida glabrata: Insights from the Vivli AMR data challenge

<ns5:p> Background Antifungal resistance is an emerging but underrecognized public health threat. It receives limited attention in global antimicrobial resistance surveillance and stewardship efforts. While growing evidence links environmental pollution to bacterial resistance, the role of pollution in driving antifungal resistance remains largely unexplored. We investigated whether prolonged exposure to ambient air pollutants is associated with increased drug resistance in <ns5:italic>Candida glabrata.</ns5:italic> Methods We performed exploratory and spatiotemporal analyses of 4,055 <ns5:italic>C. glabrata</ns5:italic> isolates collected from the U.S. and Western Europe between 2010 and 2023, as part of the Pfizer-Atlas surveillance initiative. We constructed a composite resistance phenotype based on resistance information for four antifungals: anidulafungin, caspofungin, micafungin, and fluconazole. In parallel, we extracted annual concentrations for three air pollutants, NO <ns5:sub>2</ns5:sub> , PM <ns5:sub>2.5</ns5:sub> , and PM <ns5:sub>10</ns5:sub> , from the WHO Ambient Air Quality Database (v6.1, 2024). We then assessed the association between pollutant levels and the composite resistance phenotype using time-series regression analysis. Lastly, we also evaluated the delayed effect of pollution on antifungal resistance by introducing a 1- to 3-year lag. Results Our spatiotemporal analysis revealed global increase in fluconazole resistance. In the U.S., we found a significant positive correlation between NO <ns5:sub>2</ns5:sub> and isolates that were resistant to fluconazole but sensitive to the other three antifungals. We observed a consistent increase in the proportion of these isolates in the U.S. over time, while the increase in Western Europe was variable but notable. Our time-series regression analysis indicated that even after the introduction of a time-lag, the U.S. had stronger and more consistent links between air pollutants and antifungal resistance than Western Europe. Conclusions Our study is the first of its kind to provide large-scale, data-driven evidence linking prolonged presence of air pollution with time-lagged antifungal resistance in <ns5:italic>C. glabrata.</ns5:italic> Our preliminary findings emphasize the necessity of including environmental factors in antifungal stewardship and surveillance. </ns5:p>