Do storm overflows influence AMR in the environment and is this relevant to human health? A UK perspective on a global issue.

Antimicrobial resistance (AMR) is a global public health threat, and the environment has been identified as an important reservoir for resistant microorganisms and genes. Storm overflows (SOs) discharge wastewater and stormwater, and are found throughout many wastewater networks. While there are no data currently showing the impact of SOs on the environment with respect to AMR in the UK, there is a small but growing body of evidence globally highlighting the potential role of SOs on environmental AMR. This review aims to provide an overview of the current state of SOs, describe global data investigating the impact of SOs on environmental AMR, and discuss the implications of SOs regarding AMR and human health. In addition, the complexities of studying the effects of SOs are discussed and a set of priority research questions and policy interventions to tackle a potentially emerging threat to public health are presented.

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?

The environment plays a critical role in the development, dissemination, and transmission of antimicrobial resistance (AMR). Pharmaceuticals and personal care products (PPCPs) enter the environment through direct application to the environment and through anthropogenic pollution. Although there is a growing body of evidence defining minimal selective concentrations (MSCs) of antibiotics and the role antibiotics play in horizontal gene transfer (HGT), there is limited evidence on the role of non-antibiotic PPCPs. Existing data show associations with the development of resistance or effects on bacterial growth rather than calculating selective endpoints. Research has focused on laboratory-based systems rather than in situ experiments, although PPCP concentrations found throughout wastewater, natural water, and soil environments are often within the range of laboratory-derived MSCs and at concentrations shown to promote HGT. Increased selection and HGT of AMR by PPCPs will result in an increase in total AMR abundance in the environment, increasing the risk of exposure and potential transmission of environmental AMR to humans. There is some evidence to suggest that humans can acquire resistance from environmental settings, with water environments being the most frequently studied. However, because this is currently limited, we recommend that more evidence be gathered to understand the risk the environment plays in regard to human health. In addition, we recommend that future research efforts focus on MSC-based experiments for non-antibiotic PPCPS, particularly in situ, and investigate the effect of PPCP mixtures on AMR. Environ Toxicol Chem 2022;00:1-14. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

The 'SELection End points in Communities of bacTeria' (SELECT) Method: A Novel Experimental Assay to Facilitate Risk Assessment of Selection for Antimicrobial Resistance in the Environment.

BACKGROUND: Antimicrobial resistance (AMR) is one of the most significant health threats to society. A growing body of research demonstrates selection for AMR likely occurs at environmental concentrations of antibiotics. However, no standardized experimental approaches for determining selective concentrations of antimicrobials currently exist, preventing appropriate environmental and human health risk assessment of AMR. OBJECTIVES: We aimed to design a rapid, simple, and cost-effective novel experimental assay to determine selective effect concentrations of antibiotics and to generate the largest experimental data set of selective effect concentrations of antibiotics to date. METHODS: Previously published methods and data were used to validate the assay, which determines the effect concentration based on reduction of bacterial community (wastewater) growth. Risk quotients for test antibiotics were generated to quantify risk. RESULTS: The assay (SELection End points in Communities of bacTeria, or the SELECT method) was used to rapidly determine selective effect concentrations of antibiotics. These were in good agreement with quantitative polymerase chain reaction effect concentrations determined within the same experimental system. The SELECT method predicted no effect concentrations were minimally affected by changes in the assay temperature, growth media, or microbial community used as the inoculum. The predicted no effect concentrations for antibiotics tested ranged from 0.05µg/L for ciprofloxacin to 1,250µg/L for erythromycin. DISCUSSION: The lack of evidence demonstrating environmental selection for AMR, and of associated human health risks, is a primary reason for the lack of action in the mitigation of release of antibiotics into the aquatic environment. We present a novel method that can reliably and rapidly fill this data gap to enable regulation and subsequent mitigation (where required) to lower the risk of selection for, and human exposure to, AMR in aquatic environments. In particular, ciprofloxacin and, to a lesser extent, azithromycin, cefotaxime, and trimethoprim all pose a significant risk for selection of AMR in the environment. https://doi.org/10.1289/EHP6635.

Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration.

Determining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commission's Water Framework Directive's priority hazardous substances Watch List. The macrolides demonstrated positive selection for ermF at concentrations 1-2 orders of magnitude greater (>500 and <750 µg/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for intI1 at concentrations similar to current MECs (>7.8 and <15.6 µg/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.

What is the research evidence for antibiotic resistance exposure and transmission to humans from the environment? A systematic map protocol.

BACKGROUND: Antimicrobial resistance (AMR) is a public health crisis that is predicted to cause 10 million deaths per year by 2050. The environment has been implicated as a reservoir of AMR and is suggested to play a role in the dissemination of antibiotic resistance genes (ARGs). Currently, most research has focused on measuring concentrations of antibiotics and characterising the abundance and diversity of ARGs and antibiotic resistant bacteria (ARB) in the environment. To date, there has been limited empirical research on whether humans are exposed to this, and whether exposure can lead to measureable impacts on human health. Therefore, the objective of this work is to produce two linked systematic maps to investigate previous research on exposure and transmission of AMR to humans from the environment. The first map will investigate the available research relating to exposure and transmission of ARB/ARGs from the environment to humans on a global scale and the second will investigate the prevalence of ARB/ARGs in various environments in the UK. These two maps will be useful for policy makers and research funders to identify where there are significant gluts and gaps in the current research, and where more primary and synthesis research needs to be undertaken. METHODS: Separate search strategies will be developed for the two maps. Searches will be run in 13 databases, and grey literature will be sought from key websites and engagement with experts. Hits will be managed in EndNote and screened in two stages (title/abstract then full text) against predefined inclusion criteria. A minimum of 10% will be double screened with ongoing consistency checking. All included studies will have data extracted into a bespoke form designed and piloted for each map. Data to be extracted will include bibliographic details, study design, location, exposure source, exposure route, health outcome (Map 1); and prevalence/percentage of ARB/ARG (Map 2). No validity appraisal will be undertaken. Results will be tabulated and presented narratively, together with graphics showing the types and areas of research that has been undertaken and heatmaps for key exposure-health outcomes (Map 1) and exposure-prevalence (Map 2).