Multiple Fungicide-Driven Alterations in Azole-Resistant Aspergillus fumigatus, Colombia, 2015.

Abstract

To the Editor: We read with interest the report by van der Linden et al. about the prevalence of azole-resistant Aspergillus fumigatus isolates from 19 countries, including 2 from the Americas (Brazil and the United States) (1). Recent reports have suggested a link between use of fungicides in agricultural practices and the presence of triazole-resistant A. fumigatus among azole-naive persons (2). These resistant strains harbored the TR34/L98H and TR46/Y121F/T289A mutations in the CYP51A gene and its promoter region. These novel mechanisms of resistance have been reported both in environmental and clinical samples in Europe, Asia, and Africa, suggesting a broad geographic spread. However, clinical isolates from 22 states in the United States (3) and a few isolates from Latin America (1,4) failed to show any fungicide-driven resistance in A. fumigatus in these continents, even though use of pesticides is a widespread practice in the Americas. Colombia was ranked fourth in the world in 2010 for the use of pesticides, reportedly using 14.5 tons/1,000 ha, 30% of which were fungicides (5). Among the fungicides approved by Colombia’s regulatory agency, the Colombian Agricultural Institute (6), tebuconazole and difenoconazole are largely used in the flower industry, more specifically in Cundinamarca, where 60% of Colombia’s flowers are produced. In 2015, we conducted a study for which 60 soil samples from flower fields and greenhouses were collected in the outskirts of Bogota, Cundinamarca. Samples were inoculated on Sabouraud agar at 43°C, and positive samples were screened for azole-resistance on agar supplemented with either itraconazole (4 mg/L) or voriconazole (4 mg/L). Of the 38 resistant Aspergillus strains, 20 were selected (up to 5 colonies for each positive culture), identified as A. fumigatus by β-tubulin gene sequencing, and analyzed for CYP51A gene alterations (7). Results showed great diversity in molecular resistance with the presence of TR46/Y121F/T289A (n = 17), TR34/L98H (n = 1), and TR53 (n = 1) mutations; 1 isolate had a wild-type CYP51 sequence (8). Our study highlights the presence of A. fumigatus harboring fungicide-driven alterations in Colombia, South America. The results indicate the importance of initiating active agricultural surveillance along with close monitoring of drug resistance in clinical isolates from naive and azole-exposed patients in these countries. Clinical management of Aspergillus disease can be challenging because of unfavorable clinical outcomes after patients have acquired multi-azole–resistant strains from the environment (9). Additional studies are needed to evaluate the extent to which pesticide use in floriculture and agriculture (e.g., coffee and banana) contributes to azole resistance in Colombia.