Environmental Isolates of Multi-Azole-Resistant Aspergillus spp. in Southern Italy.

Laura Trovato,Maria Domina,Salvatore Oliveri,Guido Scalia

doi:10.3390/jof4040131

Abstract

Azole resistance in Aspergillus spp. has been increasingly reported worldwide. Acquired azole resistance is probably linked to environmental exposure to fungicides used in agriculture. We collected a total of 84 soil and leaf samples from eight farms in Southern Italy. Aspergillus isolates were tested for resistance to itraconazole, posaconazole, and voriconazole by the EUCAST method. Five out of 84 samples yielded A. fumigatus isolates: four of them were itraconazole-resistant and were identified as A. fumigatus sensu stricto, three of them were posaconazole-resistant, and two were also voriconazole-resistant. All three isolates harbored the TR34/L98H resistance mechanism, which was detected by DNA sequencing of the cyp51A gene. Fifteen out of 84 samples yielded Aspergillus spp. isolates and included 11 itraconazole-resistant isolates: Aspergillus section Nigri (9) and Aspergillus section Flavi (2). Our study reports for the first time the isolation of azole-resistant A. fumigatus harboring TR34/L98H mutation from the environment of Southern Italy. The present work provides a better understanding of the magnitude of the environmental spread of azole resistance in the context of a necessary effective surveillance program to improve the management of Aspergillus-related disease.

Highlights

Aspergillus spp. are ubiquitous saprophytic fungi that commonly occur in soil, water, and decaying vegetation, producing conidia which can be dispersed to the ambient air
Triazole antifungal drugs are the major compounds currently involved in the treatment and prophylaxis of aspergillosis [8]: itraconazole, the first orally active drug for aspergillosis, is commonly used in the treatment of chronic pulmonary aspergillosis and allergic conditions [9]; voriconazole, with its oral and intravenous availability, is the first-choice therapy for invasive aspergillosis [10]; posaconazole is preferred for the prevention of invasive aspergillosis in leukemia and bone marrow transplant patients [11]; and isavuconazole has only recently been approved for the treatment of invasive aspergillosis [12]
Susceptibility testing performed by broth microdilution on the five Aspergillus section Fumigati isolates confirmed itraconazole resistance in four isolates (4/84, 4.7%) with a range of Minimum inhibitory concentration (MIC) values from 8 to >16 mg/L, while no resistance was confirmed for the fifth isolate (MIC=0.125 mg/L)

Summary

Introduction

Aspergillus spp. are ubiquitous saprophytic fungi that commonly occur in soil, water, and decaying vegetation, producing conidia which can be dispersed to the ambient air. Inhalation of such conidia, in association with certain risk conditions, can trigger aspergillosis, a group of several pulmonary diseases in humans, ranging from allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and aspergilloma to the most severe form, invasive aspergillosis (IA) [1,2].

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