Antifungal Exposure and Resistance Development: Defining Minimal Selective Antifungal Concentrations and Testing Methodologies

Abstract

This scoping review aims to summarise the current understanding of selection for antifungal resistance (AFR) and to compare and contrast this with selection for antibacterial resistance, which has received more research attention. AFR is an emerging global threat to human health, associated with high mortality rates, absence of effective surveillance systems and with few alternative treatment options available. Clinical AFR is well documented, with additional settings increasingly being recognised to play a role in the evolution and spread of AFR. The environment, for example, harbours diverse fungal communities that are regularly exposed to antifungal micropollutants, potentially increasing AFR selection risk. The direct application of effect concentrations of azole fungicides to agricultural crops and the incomplete removal of pharmaceutical antifungals in wastewater treatment systems are of particular concern. Currently, environmental risk assessment (ERA) guidelines do not require assessment of antifungal agents in terms of their ability to drive AFR development, and there are no established experimental tools to determine antifungal selective concentrations. Without data to interpret the selective risk of antifungals, our ability to effectively inform safe environmental thresholds is severely limited. In this review, potential methods to generate antifungal selective concentration data are proposed, informed by approaches used to determine antibacterial minimal selective concentrations. Such data can be considered in the development of regulatory guidelines that aim to reduce selection for AFR.

The conjunctival fungal microflora of horses in a North Queensland tropical environment and their in vitro susceptibilities to antifungal agents

“…Fungal communities are adaptive and may develop resistance after being exposed to antifungals, making infections harder to treat (Anderson 2005;Ksiezopolska and Gabaldon 2018;Odds et al 2003;Perlin et al 2017;Revie et al 2018). Antifungal resistance can develop because of regular exposure to increased antifungal micropollutants in the environment nowadays (Stevenson et al 2022). There are several ways that antifungals can get into the environment.…”

Does Environmental Exposure to Pharmaceutical and Personal Care Product Residues Result in the Selection of Antimicrobial-Resistant Microorganisms, and is this Important in Terms of Human Health Outcomes?

“…However, Khan et al (2017) determined multiple MSCs for the disinfectants chlorine and monochloramine using single‐species competition assays. In addition, a recent review compared laboratory methodologies used to define MSCs for antibiotics and discussed the strengths and weaknesses of these in relation to their use in defining antifungal MSCs for antifungal resistance (Stevenson et al, 2022).…”

A One Health approach to overcoming fungal disease and antifungal resistance

“…Typically, the recovery of antifungal resistant isolates from infected patients lacking prior exposure to antifungal agents suggests alternative routes of resistance acquisition (Bastos et al, 2021). In addition, mapping selection of antifungal resistance compared to antibacterial resistance, with the latter being extensively well-studied, provides a foundation for exploring the connection between environment (e.g., agricultural crops treated with fungicides) and health (e.g., wastewater contaminated with pharmaceutical antifungals; Stevenson et al, 2022). Moreover, the lack of environmental risk assessment guidelines toward antifungal agents and the drive toward resistance provides an incomplete correlative picture for countries to act against.…”