The Complex Interplay Between Antibiotic Resistance and Pharmaceutical and Personal Care Products in the Environment.

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are important environmental contaminants. Nonetheless, what drives the evolution, spread, and transmission of antibiotic resistance dissemination is still poorly understood. The abundance of ARB and ARGs is often elevated in human-impacted areas, especially in environments receiving fecal wastes, or in the presence of complex mixtures of chemical contaminants, such as pharmaceuticals and personal care products. Self-replication, mutation, horizontal gene transfer, and adaptation to different environmental conditions contribute to the persistence and proliferation of ARB in habitats under strong anthropogenic influence. Our review discusses the interplay between chemical contaminants and ARB and their respective genes, specifically in reference to co-occurrence, potential biostimulation, and selective pressure effects, and gives an overview of mitigation by existing man-made and natural barriers. Evidence and strategies to improve the assessment of human health risks due to environmental antibiotic resistance are also discussed. Environ Toxicol Chem 2023;00:1-16. © 2022 SETAC.

Research needs for optimising wastewater-based epidemiology monitoring for public health protection.

Wastewater-based epidemiology (WBE) is an unobtrusive method used to observe patterns in illicit drug use, poliovirus, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The pandemic and need for surveillance measures have led to the rapid acceleration of WBE research and development globally. With the infrastructure available to monitor SARS-CoV-2 from wastewater in 58 countries globally, there is potential to expand targets and applications for public health protection, such as other viral pathogens, antimicrobial resistance (AMR), pharmaceutical consumption, or exposure to chemical pollutants. Some applications have been explored in academic research but are not used to inform public health decision-making. We reflect on the current knowledge of WBE for these applications and identify barriers and opportunities for expanding beyond SARS-CoV-2. This paper critically reviews the applications of WBE for public health and identifies the important research gaps for WBE to be a useful tool in public health. It considers possible uses for pathogenic viruses, AMR, and chemicals. It summarises the current evidence on the following: (1) the presence of markers in stool and urine; (2) environmental factors influencing persistence of markers in wastewater; (3) methods for sample collection and storage; (4) prospective methods for detection and quantification; (5) reducing uncertainties; and (6) further considerations for public health use.

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).

A cross-sectional study on the prevalence of illness in coastal bathers compared to non-bathers in England and Wales: Findings from the Beach User Health Survey.

The risks of illness associated with bathing in UK coastal waters have not been quantified since the early 1990s. Efforts have been made since then to improve the quality of bathing waters. The aim of this study was to quantify the prevalence of symptoms of illness associated with sea bathing in bathers in England and Wales. A cross-sectional study was conducted between June 2014 and April 2015. An online survey collected information from sea bathers and non-bathers on their visits to beaches in England and Wales along with the occurrence of symptoms of illness. 2631 people (1693 bathers, 938 non-bathers) responded to the survey. Compared to non-bathers, bathers were more likely to report skin ailments (adjusted prevalence odds ratio (AOR) = 2.64, 95% confidence interval (CI) 1.23 to 5.65, p = 0.01), ear ailments (AOR = 3.77, 95% CI 1.84 to 7.73, p < 0.001), and any symptoms of illness (AOR = 3.73, 95% CI 2.63 to 5.29, p < 0.001). There was weak evidence of an increase in the odds of gastrointestinal illness (AOR = 1.59, 95% CI 0.96 to 2.65, p = 0.07), respiratory ailments (AOR = 2.44, 95% CI 0.92 to 6.48, p = 0.07) and eye ailments (AOR = 2.12, 95% CI 0.83 to 5.39, p = 0.11). While the study design does not allow inference of causality, we do observe an association between sea bathing in England and Wales and reported symptoms of ill health. This suggests that despite higher rates of compliance with water quality criteria among bathing waters nowadays, the odds of illness for bathers relative to non-bathers is similar in magnitude to estimates made in the 1990s.

Is it safe to go back into the water? A systematic review and meta-analysis of the risk of acquiring infections from recreational exposure to seawater.

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.

Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water users: Environmental surveillance, exposure assessment, and epidemiological study (Beach Bum Survey).

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.

Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters.

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.