Dawning of a new ERA: Environmental Risk Assessment of antibiotics and their potential to select for antimicrobial resistance.

Antibiotics and antimicrobials are used, misused and overused in human and veterinary medicine, animal husbandry and aquaculture. These compounds can persist in both human and animal waste and then enter the environment through a variety of mechanisms. Though generally measured environmental concentrations (MECs) of antibiotics in aquatic systems are significantly lower than point of therapeutic use concentrations, there is increasing evidence that suggests these concentrations may still enrich antimicrobial resistant bacteria. In light of this evidence, a rigorous and standardised novel methodology needs to be developed which can perform environmental risk assessment (ERA) of antimicrobials in terms of their selective potential as well as their environmental impact, to ensure that diffuse and point source discharges are safe. This review summarises and critically appraises the current methodological approaches that study selection at below point of therapeutic use, or sub-inhibitory, concentrations of antibiotics. We collate and compare selective concentration data generated to date. We recommend how these data can be interpreted in line with current ERA guidelines; outlining and describing novel concepts unique to risk assessment of AMR (such as direct selection of AMR or increased persistence of AMR). We consolidate terminology used thus far into a single framework that could be adopted moving forward, by proposing predicted no effect concentrations for resistance (PNECRs) and predicted no effect concentrations for persistence (PNECPs) be determined in AMR risk assessment. Such a framework will contribute to antibiotic stewardship and by extension, protection of human health, food security and the global economy.