Alteração no perfil de susceptibilidade de Aspergillus flavus a antifúngicos clínicos após exposição a agrotóxicos

Abstract

Resistance to azole antifungals in Aspergillus has been reported in several countries. The development of resistance compromises therapy and increases the likelihood of therapeutic failure. The hypothesis of an environmental origin of resistance has been proposed and associated with the use of azole pesticides in the environment since azole pesticides are chemically similar to the azole antifungals used in the clinic. In this context, environmental fungi considered human pathogens, such as Aspergillus flavus, may develop cross-resistance. The aim of this study was to evaluate the change in the clinical antifungal susceptibility profile of Aspergillus flavus strains after exposure to pesticides. The susceptibility testing was performed according to the CLSI M38-A2 protocol, and the microorganisms were exposed to the pesticides for 28 days. The antifungals itraconazole, voriconazole and posaconazole were tested at concentrations ranging from 0.313 to 16 μg/mL. The pesticides thiabendazole, tebuconazole and metconazole were used during the fungal exposure period. In addition, an evaluation of the macromorphological characteristics of the colonies was carried out. Exposure to pesticides altered the susceptibility profile for the antifungal agents itraconazole, voriconazole and posaconazole; this change was characterized by an increase in the MIC of up to 16, 16 and 32 times, respectively, evidencing the development of resistance phenotypes. The most significant changes were found after exposure to a pool of the pesticides; these changes are reported here for the first time. For the combination of metconazole, tebuconazole and thiabendazole, an increase in the MIC of 256 times was observed. This result indicates a synergistic action among azole compounds that potentiates the development of cross-resistance. In addition, exposure to pesticides changed the pigmentation of the colonies from green to white. The development of cross-resistance generates great concern in the medical community because cross-resistance is associated with risks to human health, azole pesticides are used indiscriminately, and a single application often includes more than one azole compound.