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      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

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          Abstract

          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 μ g / L for ciprofloxacin to 1,250 μ g / 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

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          Most cited references25

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          STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT

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            Understanding Bland Altman analysis

            In a contemporary clinical laboratory it is very common to have to assess the agreement between two quantitative methods of measurement. The correct statistical approach to assess this degree of agreement is not obvious. Correlation and regression studies are frequently proposed. However, correlation studies the relationship between one variable and another, not the differences, and it is not recommended as a method for assessing the comparability between methods.
In 1983 Altman and Bland (B&A) proposed an alternative analysis, based on the quantification of the agreement between two quantitative measurements by studying the mean difference and constructing limits of agreement.
The B&A plot analysis is a simple way to evaluate a bias between the mean differences, and to estimate an agreement interval, within which 95% of the differences of the second method, compared to the first one, fall. Data can be analyzed both as unit differences plot and as percentage differences plot.
The B&A plot method only defines the intervals of agreements, it does not say whether those limits are acceptable or not. Acceptable limits must be defined a priori, based on clinical necessity, biological considerations or other goals.
The aim of this article is to provide guidance on the use and interpretation of Bland Altman analysis in method comparison studies.
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              Is Open Access

              Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution

              Around all human activity, there are zones of pollution with pesticides, heavy metals, pharmaceuticals, personal care products and the microorganisms associated with human waste streams and agriculture. This diversity of pollutants, whose concentration varies spatially and temporally, is a major challenge for monitoring. Here, we suggest that the relative abundance of the clinical class 1 integron-integrase gene, intI1, is a good proxy for pollution because: (1) intI1 is linked to genes conferring resistance to antibiotics, disinfectants and heavy metals; (2) it is found in a wide variety of pathogenic and nonpathogenic bacteria; (3) its abundance can change rapidly because its host cells can have rapid generation times and it can move between bacteria by horizontal gene transfer; and (4) a single DNA sequence variant of intI1 is now found on a wide diversity of xenogenetic elements, these being complex mosaic DNA elements fixed through the agency of human selection. Here we review the literature examining the relationship between anthropogenic impacts and the abundance of intI1, and outline an approach by which intI1 could serve as a proxy for anthropogenic pollution.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ Health Perspect
                EHP
                Environmental Health Perspectives
                Environmental Health Perspectives
                0091-6765
                1552-9924
                21 October 2020
                October 2020
                : 128
                : 10
                : 107007
                Affiliations
                [ 1 ]European Centre for Environment and Human Health, University of Exeter Medical School , Cornwall, UK
                [ 2 ]Environment and Sustainability Institute, University of Exeter Medical School , Cornwall, UK
                [ 3 ]AstraZeneca Global Environment , Macclesfield, UK
                Author notes
                Address correspondence to Aimee K. Murray, European Centre for Environment and Human Health, Environment and Sustainability Institute, University of Exeter Medical School, Penryn Campus, Cornwall, TR10 9FE, UK. Email: a.k.murray@ 123456exeter.ac.uk
                Article
                EHP6635
                10.1289/EHP6635
                7577113
                33084388
                22ca6976-1928-4273-967f-299643d42406

                EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.

                History
                : 06 December 2019
                : 23 September 2020
                : 25 September 2020
                Categories
                Research

                Public health
                Public health

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