Abstract
. 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.
.

Antimicrobial resistance (AMR) is widely recognised as a considerable threat to human health, wellbeing and prosperity. Many clinically important antibiotic resistance genes are understood to have originated in the natural environment. However, the complex interactions between humans, animals and the environment makes the health implications of environmental AMR difficult to quantify. This narrative review focuses on the current state of knowledge regarding antibiotic resistant bacteria (ARB) in natural bathing waters and implications for human health. It considers the latest research focusing on the transmission of ARB from bathing waters to humans. The limitations of existing evidence are discussed, as well as research priorities. The authors are of the opinion that future studies should include faecally contaminated bathing waters and people exposed to these environments to accurately parameterise environment-to-human transmission.

Abstract
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).

© FEMS 2018. Antimicrobial resistance and the spread of antibiotic resistance genes (ARGs) pose a threat to human health. Community-acquired infections resistant to treatment with first-line antibiotics are increasing, and there are few studies investigating environmental exposures and transmission. Our objective is to develop a novel targeted metagenomic method to quantify the abundance and diversity of ARGs in a faecal indicator bacterium, and to estimate human exposure to resistant bacteria in a natural environment. Sequence data from Escherichia coli metagenomes from 13 bathing waters in England were analysed using the ARGs Online Analysis Pipeline to estimate the abundance and diversity of resistance determinants borne by this indicator bacterium. These data were averaged over the 13 sites and used along with data on the levels of E. coli in English bathing waters in 2016 and estimates of the volume of water that water users typically ingest in an average session of their chosen activityto quantify the numbers of ARGs that water users ingest. Escherichia coli in coastal bathing waters were found to harbour on average 1.24 ARGs per cell. Approximately 2.5 million water sports sessions occurred in England in 2016 that resulted in water users ingesting at least 100 E. coli-borne ARGs.

BACKGROUND: Antibiotic-resistant bacteria (ARB) present a global public health problem. With numbers of community-acquired resistant infections increasing, understanding the mechanisms by which people are exposed to and colonised by ARB can help inform effective strategies to prevent their spread. The role natural environments play in this is poorly understood. This is the first study to combine surveillance of ARB in bathing waters, human exposure estimates and association between exposure and colonisation by ARB in water users. METHODS: 97 bathing water samples from England and Wales were analysed for the proportion of E. coli harbouring blaCTX-M. These data were used to estimate the likelihood of water users ingesting blaCTX-M-bearing E. coli. Having identified surfers as being at risk of exposure to ARB, a cross-sectional study was conducted. Regular surfers and non-surfers were recruited to assess whether there is an association between surfing and gut colonisation by blaCTX-M-bearing E. coli. RESULTS: 11 of 97 bathing waters sampled were found to contain blaCTX-M-bearing E. coli. While the percentage of blaCTX-M-bearing E. coli in bathing waters was low (0.07%), water users are at risk of ingesting these ARB. It is estimated that over 2.5 million water sports sessions occurred in 2015 resulting in the ingestion of at least one blaCTX-M-bearing E. coli. In the epidemiological survey, 9/143 (6.3%) surfers were colonised by blaCTX-M-bearing E. coli, as compared to 2/130 (1.5%) of non-surfers (risk ratio=4.09, 95% CI 1.02 to 16.4, p=0.046). CONCLUSIONS: Surfers are at risk of exposure to and colonisation by clinically important antibiotic-resistant E. coli in coastal waters. Further research must be done on the role natural environments play in the transmission of ARB.

Background: Numerous illnesses are associated with bathing in natural waters, although it is assumed that the risk of illness among bathers exposed to relatively clean waters found in high-income countries is negligible. A systematic review was carried out to quantify the increased risk of experiencing a range of adverse health outcomes among bathers exposed to coastal water compared with non-bathers. Methods: in all 6919 potentially relevant titles and abstracts were screened, and from these 40 studies were eligible for inclusion in the review. Odds ratios (OR) were extracted from 19 of these reports and combined in random-effect meta-analyses for the following adverse health outcomes: incident cases of any illness, ear infections, gastrointestinal illness and infections caused by specific microorganisms. Results: There is an increased risk of experiencing symptoms of any illness [OR = 1.86, 95% confidence interval (CI): 1.31 to 2.64, P = 0.001] and ear ailments (OR = 2.05, 95% CI: 1.49 to 2.82, P < 0.001) in bathers compared with non-bathers. There is also an increased risk of experiencing gastrointestinal ailments (OR = 1.29, 95% CI: 1.12 to 1.49, P < 0.001). Conclusions: This is the first systematic review to evaluate evidence on the increased risk of acquiring illnesses from bathing in seawater compared with non-bathers. Our results support the notion that infections are acquired from bathing in coastal waters, and that bathers have a greater risk of experiencing a variety of illnesses compared with non-bathers.

Infections caused by antibiotic resistant bacteria (ARB) are associated with poor health outcomes and are recognised globally as a serious health problem. Much research has been conducted on the transmission of ARB to humans. Yet the role the natural environment plays in the spread of ARB and antibiotic resistance genes is not well understood. Antibiotic resistant bacteria have been detected in natural aquatic environments, and ingestion of seawater during water sports is one route by which many people could be directly exposed. The aim was to estimate the prevalence of resistance to one clinically important class of antibiotics (third-generation cephalosporins (3GCs)) amongst Escherichia coli in coastal surface waters in England and Wales. Prevalence data was used to quantify ingestion of 3GC-resistant E. coli (3GCREC) by people participating in water sports in designated coastal bathing waters. A further aim was to use this value to derive a population-level estimate of exposure to these bacteria during recreational use of coastal waters in 2012. The prevalence of 3GC-resistance amongst E. coli isolated from coastal surface waters was estimated using culture-based methods. This was combined with the density of E. coli reported in designated coastal bathing waters along with estimations of the volumes of water ingested during various water sports reported in the literature to calculate the mean number of 3GCREC ingested during different water sports.0.12% of E. coli isolated from surface waters were resistant to 3GCs. This value was used to estimate that in England and Wales over 6.3 million water sport sessions occurred in 2012 that resulted in the ingestion of at least one 3GCREC.Despite the low prevalence of resistance to 3GCs amongst E. coli in surface waters, there is an identifiable human exposure risk for water users, which varies with the type of water sport undertaken. The relative importance of this exposure is likely to be greater in areas where a large proportion of the population enjoys water sports. Millions of water sport sessions occurred in 2012 that were likely to have resulted in people ingesting E. coli resistant to a single class of antibiotics (3GCs). However, this is expected to be a significant underestimate of recreational exposure to all ARB in seawater. This is the first study to use volumes of water ingested during different water sports to estimate human exposure to ARB. Further work needs to be done to elucidate the health implications and clinical relevance of exposure to ARB in both marine and fresh waters in order to fully understand the risk to public health.

© 2015 Elsevier Ltd. Infections caused by antibiotic resistant bacteria (ARB) are associated with poor health outcomes and are recognised globally as a serious health problem. Much research has been conducted on the transmission of ARB to humans. Yet the role the natural environment plays in the spread of ARB and antibiotic resistance genes is not well understood. Antibiotic resistant bacteria have been detected in natural aquatic environments, and ingestion of seawater during water sports is one route by which many people could be directly exposed.The aim was to estimate the prevalence of resistance to one clinically important class of antibiotics (third-generation cephalosporins (3GCs)) amongst Escherichia coli in coastal surface waters in England and Wales. Prevalence data was used to quantify ingestion of 3GC-resistant E. coli (3GCREC) by people participating in water sports in designated coastal bathing waters. A further aim was to use this value to derive a population-level estimate of exposure to these bacteria during recreational use of coastal waters in 2012.The prevalence of 3GC-resistance amongst E. coli isolated from coastal surface waters was estimated using culture-based methods. This was combined with the density of E. coli reported in designated coastal bathing waters along with estimations of the volumes of water ingested during various water sports reported in the literature to calculate the mean number of 3GCREC ingested during different water sports.0.12% of E. coli isolated from surface waters were resistant to 3GCs. This value was used to estimate that in England and Wales over 6.3 million water sport sessions occurred in 2012 that resulted in the ingestion of at least one 3GCREC.Despite the low prevalence of resistance to 3GCs amongst E. coli in surface waters, there is an identifiable human exposure risk for water users, which varies with the type of water sport undertaken. The relative importance of this exposure is likely to be greater in areas where a large proportion of the population enjoys water sports. Millions of water sport sessions occurred in 2012 that were likely to have resulted in people ingesting E. coli resistant to a single class of antibiotics (3GCs). However, this is expected to be a significant underestimate of recreational exposure to all ARB in seawater.This is the first study to use volumes of water ingested during different water sports to estimate human exposure to ARB. Further work needs to be done to elucidate the health implications and clinical relevance of exposure to ARB in both marine and fresh waters in order to fully understand the risk to public health.