Antifungal azoles and azole resistance in the environment: current status and future perspectives—a review

Following their extensive use, azole antifungals may enter the environment through the discharge of domestic, industrial and hospital wastewaters, agricultural runoffs and as leachates in waste-disposal sites. The presence of the azole antifungals poses potential toxicity risks to non-target organisms and plays a critical role in the evolution and/or selection of azole resistant fungal strains in the environment. Toxicities such as inhibition of algal growth, endocrine disruption in fish, CYP450-effected steroidogenesis, modulating sex differentiation in frogs, and reduction of larval body mass and growth rate have been related to azole antifungals. In addition, the isolation of azole resistant fungi such as Aspergillus fumigatus in both the environment and clinic retaining similar mode of molecular drug resistance mechanism has drawn the attention of many researchers. Therefore, the investigation of the occurrence and distribution of azole antifungals as well as azole resistant environmental isolates of fungi is becoming a trendy research venue. Here we review the occurrence of antifungal azoles and azole resistance in the environment. The major points discussed are (1) an update on the environmental occurrence, distribution and ecological risks of the most commonly used azole antifungals in the environment including surface water and drinking water (2) environmental azole antifungal resistance, predominant molecular mechanisms of azole resistance in the environment, and the implications for human health (3) future trends and perspectives that could help reduce the ecological and human health risks of azoles and tackle the spread of azole resistance in the environment, and hence in the clinic.