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 Commissionʼs 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.
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 0:05 lg=L for ciprofloxacin to 1,250 lg=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.
Clinical testing of children in schools is challenging, with economic implications limiting its frequent use as a monitoring tool of the risks assumed by children and staff during the COVID-19 pandemic. Here, a wastewater-based epidemiology approach has been used to monitor 16 schools (10 primary, 5 secondary and 1 post-16 and further education) in England. A total of 296 samples over 9 weeks have been analysed for N1 and E genes using qPCR methods. Of the samples returned, 47.3% were positive for one or both genes with a detection frequency in line with the respective local community. WBE offers a low cost, non-invasive approach for supplementing clinical testing and can provide longitudinal insights that are impractical with traditional clinical testing.
Background Antimicrobial resistance (AMR) is predicted to become the leading cause of death by 2050 with antibiotic resistance being an important component. Anthropogenic pollution introduces antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to the natural environment. Currently, there is limited empirical evidence demonstrating whether humans are exposed to environmental AMR and whether this exposure can result in measurable human health outcomes. In recent years there has been increasing interest in the role of the environment and disparate evidence on transmission of AMR to humans has been generated but there has been no systematic attempt to summarise this. We aim to create two systematic maps that will collate the evidence for (1) the transmission of antibiotic resistance from the natural environment to humans on a global scale and (2) the state of antibiotic resistance in the environment in the United Kingdom. Methods Search strategies were developed for each map. Searches were undertaken in 13 bibliographic databases. Key websites were searched and experts consulted for grey literature. Search results were managed using EndNote X8. Titles and abstracts were screened, followed by the full texts. Articles were double screened at a minimum of 10% at both stages with consistency checking and discussion when disagreements arose. Data extraction occurred in Excel with bespoke forms designed. Data extracted from each selected study included: bibliographic information; study site location; exposure source; exposure route; human health outcome (Map 1); prevalence/percentage/abundance of ARB/antibiotic resistance elements (Map 2) and study design. EviAtlas was used to visualise outputs. Results For Map 1, 40 articles were included, from 11,016 unique articles identified in searches, which investigated transmission of AMR from the environment to humans. Results from Map 1 showed that consumption/ingestion was the most studied transmission route. Exposure (n = 17), infection (n = 16) and colonisation (n = 11) being studied as an outcome a similar number of times, with mortality studied infrequently (n = 2). In addition, E. coli was the most highly studied bacterium (n = 16). For Map 2, we included 62 studies quantifying ARB or resistance elements in the environment in the UK, from 6874 unique articles were identified in the searches. The most highly researched species was mixed communities (n = 32). The most common methodology employed in this research question was phenotypic testing (n = 37). The most commonly reported outcome was the characterisation of ARBs (n = 40), followed by characterisation of ARGs (n = 35). Other genetic elements, such as screening for intI1 (n = 15) (which encodes a Class 1 integron which is used as a proxy for environmental ARGs) and point mutations (n = 1) were less frequently reported. Both maps showed that research was focused towards aquatic environments. Conclusions Both maps can be used by policy makers to show the global (Map 1) and UK (Map 2) research landscapes and provide an overview of the state of AMR in the environment and human health impacts of interacting with the environment. We have also identified (1) clusters of research which may be used to perform meta-analyses and (2) gaps in the evidence base where future primary research should focus.
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