Genesis of Azole Antifungal Resistance from Agriculture to Clinical Settings

Abstract

Azole fungal resistance is becoming a major public health problem in medicine in recent years. However, it was known in agriculture since several decades; the extensive use of these compounds results in contamination of air, plants, and soil. The increasing frequency of life-threatening fungal infections and the increase of prophylactical use of azoles in high-risk patients, taken together with the evolutionary biology evidence that drug selection pressure is an important factor for the emergence and spread of drug resistance, can result in a dramatic scenario. This study reviews the azole use in agricultural and medical contexts and discusses the hypothetical link between its extensive use and the emergence of azole resistance among human fungal pathogens.

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

“…Today, they are the most used antifungals because of their high efficiency and broad spectrum activity (Price et al, 2015) ( Table 1 ). The current use rates for many triazoles, which are the largest class of azole antifungals used nowadays, are below/or around 100 g/ha of plant surface (Morton and Staub, 2008; Azevedo et al, 2015). …”

“…Azole antifungals are part of the Sterol Biosynthesis Inhibitors (SBI) (Azevedo et al, 2015). They affect the same target in fungal cells.…”

“…The development of antiviral, antibiotics and antifungals has allowed overcoming the effect of phytopathogens but may have considerable negative impact on the environment, mainly with regard to the contamination of surface water and groundwater (Azevedo et al, 2015). Focusing on fungal pathogens, there are a number of antimycotic compounds available to control the spread of these pathogens.…”

Antibacterial and antifungal activities of pyroligneous acid from wood of Eucalyptus urograndis and Mimosa tenuiflora

“…In both the agricultural and the medical area, an increasing antifungal resistance, from the 1960 decade to the present day, is highlighted by Azevedo et al . ().…”

For Debate: May the Use of the Polyene Macrolide Natamycin as a Food Additive Foster Emergence of Polyene-Resistance in Candida Species?

“…Although the overall level of resistance to antifungal agents is still low, studies have revealed that azole-resistance and surprisingly-Amphothericin B-resistance, too, could indeed be detected in environmental strains of Aspergillus fumigatus [6][7][8][9][10][11] as well as in environmental Candida spp. Strains [12][13][14][15]. These studies indicate that the extensive agricultural use of antifungals triggers resistance development in environmental fungi beyond the limits of structural classes of antimycotics thus probably creating a threat to human health.…”