Antifungal medicines in the terrestrial environment: Levels in biosolids from England and Wales.

Antifungals are used widely in clinical and agricultural practice to control fungal growth, either treating or preventing infection. There are reports of increasing prevalence of resistance to antifungals in human pathogens and concern that their use in agriculture is driving clinical resistance in patients. While crop protection products are the most obvious source in agriculture, a further source may be biosolids from wastewater treatment. In the UK, these are applied to land to provide nutrients and improve soil structure for crops. In this study, biosolids from ten sites in England and one in Wales were analysed for clinical antifungals. Ketoconazole and miconazole were detected in all samples with a median concentration of 0.87 and 0.54 mg kg dry weight (DW), respectively. Clotrimazole was detected at seven of eleven sites at a median level of 1.32 mg kg DW and its absence at four others was considered treatment related. Two prescription-only and systemic medications, itraconazole and posaconazole, were frequently detected with median concentrations of 0.14 mg kg DW and 0.09 mg kg DW, respectively. The biosolid levels of itraconazole found in this study were two orders of magnitude higher than an indicative Predicted No Effect Concentration for resistance selection (PNEC-R) in soil. Neither fluconazole, griseofulvin, and voriconazole nor flucytosine and nystatin were found above the limit of detection of 0.01 or 0.1 mg kg as received, respectively. The findings show that biosolids represent a viable pathway for antifungal agents to reach soil.