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650600.9911Mitigating antimicrobial resistance through effective hospital wastewater management in low- and middle-income countries. Hospital wastewater (HWW) is a significant environmental and public health threat, containing high levels of pollutants such as antibiotic-resistant bacteria (ARB), antibiotic-resistant genes (ARGs), antibiotics, disinfectants, and heavy metals. This threat is of particular concern in low- and middle-income countries (LMICs), where untreated effluents are often used for irrigating vegetables crops, leading to direct and indirect human exposure. Despite being a potential hotspot for the spread of antimicrobial resistance (AMR), existing HWW treatment systems in LMICs primarily target conventional pollutants and lack effective standards for monitoring the removal of ARB and ARGs. Consequently, untreated or inadequately treated HWW continues to disseminate ARB and ARGs, exacerbating the risk of AMR proliferation. Addressing this requires targeted interventions, including cost-effective treatment solutions, robust AMR monitoring protocols, and policy-driven strategies tailored to LMICs. This perspective calls for a paradigm shift in HWW management in LMIC, emphasizing the broader implementation of onsite treatment systems, which are currently rare. Key recommendations include developing affordable and contextually adaptable technologies for eliminating ARB and ARGs and enforcing local regulations for AMR monitoring and control in wastewater. Addressing these challenges is essential for protecting public health, preventing the environmental spread of resistance, and contributing to a global effort to preserve the efficacy of antibiotics. Recommendations include integrating scalable onsite technologies, leveraging local knowledge, and implementing comprehensive AMR-focused regulatory frameworks.202439944563
668610.9906The Impact of Wastewater on Antimicrobial Resistance: A Scoping Review of Transmission Pathways and Contributing Factors. BACKGROUND/OBJECTIVES: Antimicrobial resistance (AMR) is a global issue driven by the overuse of antibiotics in healthcare, agriculture, and veterinary settings. Wastewater and treatment plants (WWTPs) act as reservoirs for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). The One Health approach emphasizes the interconnectedness of human, animal, and environmental health in addressing AMR. This scoping review analyzes wastewater's role in the AMR spread, identifies influencing factors, and highlights research gaps to guide interventions. METHODS: This scoping review followed the PRISMA-ScR guidelines. A comprehensive literature search was conducted across the PubMed and Web of Science databases for articles published up to June 2024, supplemented by manual reference checks. The review focused on wastewater as a source of AMR, including hospital effluents, industrial and urban sewage, and agricultural runoff. Screening and selection were independently performed by two reviewers, with conflicts resolved by a third. RESULTS: Of 3367 studies identified, 70 met the inclusion criteria. The findings indicated that antibiotic residues, heavy metals, and microbial interactions in wastewater are key drivers of AMR development. Although WWTPs aim to reduce contaminants, they often create conditions conducive to horizontal gene transfer, amplifying resistance. Promising interventions, such as advanced treatment methods and regulatory measures, exist but require further research and implementation. CONCLUSIONS: Wastewater plays a pivotal role in AMR dissemination. Targeted interventions in wastewater management are essential to mitigate AMR risks. Future studies should prioritize understanding AMR dynamics in wastewater ecosystems and evaluating scalable mitigation strategies to support global health efforts.202540001375
665320.9902Making waves: How does the emergence of antimicrobial resistance affect policymaking? This article considers current trends in antimicrobial resistance (AMR) research and knowledge gaps relevant to policymaking in the water sector. Specifically, biological indicators of AMR (antibiotic-resistant bacteria and their resistance genes) and detection methods that have been used so far are identified and discussed, as well as the problems with and solutions to the collection of AMR data, sewage surveillance lessons from the COVID-19 pandemic, and the financial burden caused by AMR, which could be synergically used to improve advocacy on AMR issues in the water sector. Finally, this article proposes solutions to overcoming existing hurdles and shortening the time it will take to have an impact on policymaking and regulation in the sector.202134688095
668830.9902Antibiotic resistant bacteria: A bibliometric review of literature. Antibiotic-resistant bacteria (ARB) are a serious threat to the health of people and the ecological environment. With this problem becoming more and more serious, more countries made research on the ARB, and the research number has been sharply increased particularly over the past decade. Therefore, it is quite necessary to globally retrace relevant researches on the ARB published from 2010 to 2020. This will help researchers to understand the current research situation, research trends and research hotspots in this field. This paper uses bibliometrics to examine publications in the field of ARB from 2010 to 2020 that were retrieved from the Web of Science (WOS). Our study performed a statistical analysis of the countries, institutions, journals, authors, research areas, author keywords, Essential Science Indicators (ESI) highly cited papers, and ESI hotspots papers to provide an overview of the ARB field as well as research trends, research hotspots, and future research directions in the field. The results showed that the number of related studies is increasing year by year; the USA is most published in the field of ARB; China is the most active in this field in the recent years; the Chinese Acad Sci published the most articles; Sci. Total Environ. published the greatest number of articles; CM Manaia has the most contributions; Environmental Sciences and Ecology is the most popular research area; and "antibiotic resistance," "antibiotics," and "antibiotic resistance genes" were the most frequently occurring author keywords. A citation analysis showed that aquatic environment-related antibiotic resistance is a key research area in this field, while antimicrobial nanomaterial-related research is a recent popular topic.202236466520
855340.9902Unveiling the power of nanotechnology: a novel approach to eliminating antibiotic-resistant bacteria and genes from municipal effluent. The increasing global population and declining freshwater resources have heightened the urgency of ensuring safe and accessible water supplies.Query The persistence of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in municipal effluents poses a significant public health threat, exacerbated by the widespread use of antibiotics and the inadequate removal of contaminants in wastewater treatment facilities. Conventional treatment methods often fail to eliminate these emerging pollutants, facilitating their entry into agricultural systems and natural water bodies, thereby accelerating the spread of antimicrobial resistance. To address these challenges, interdisciplinary strategies in water treatment are essential. Nanotechnology has emerged as a promising approach due to its unique physicochemical properties, biocompatibility, and high efficiency in detecting and removing biological and chemical contaminants. Various nanomaterials, including graphene-based structures, Carbon nanotubes (CNTs), noble metal nanoparticles (gold (Au) and silver (Ag)), silicon and chitosan-based nanomaterials, as well as titanium and Zinc oxide (ZnO) nanomaterials, demonstrate potent antimicrobial effects. Moreover, nanosensors and photocatalysts utilizing these nanomaterials enable precise detection and effective degradation of ARB and ARGs in wastewater. This review examines the mechanisms by which nanotechnology-based materials can mitigate the risks associated with antibiotic resistance in urban effluents, focusing on their applications in pathogen detection, pollutant removal, and wastewater treatment. By integrating nanotechnology into existing treatment frameworks, we can significantly enhance the efficiency of water purification processes, ultimately contributing to global water security and the protection of public health.202540512401
908350.9902ARGNet: using deep neural networks for robust identification and classification of antibiotic resistance genes from sequences. BACKGROUND: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing. RESULTS: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG. CONCLUSIONS: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract.202438725076
639460.9901Potential Environmental and Human Health Risks Caused by Antibiotic-Resistant Bacteria (ARB), Antibiotic Resistance Genes (ARGs) and Emerging Contaminants (ECs) from Municipal Solid Waste (MSW) Landfill. The disposal of municipal solid waste (MSW) directly at landfills or open dump areas, without segregation and treatment, is a significant concern due to its hazardous contents of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and metal resistance genes (MGEs). The released leachate from landfills greatly effects the soil physicochemical, biological, and groundwater properties associated with agricultural activity and human health. The abundance of ARB, ARGs, and MGEs have been reported worldwide, including MSW landfill sites, animal husbandry, wastewater, groundwater, soil, and aerosol. This review elucidates the occurrence and abundance of ARB, ARGs, and MRGs, which are regarded as emerging contaminants (ECs). Recently, ECs have received global attention because of their prevalence in leachate as a substantial threat to environmental and public health, including an economic burden for developing nations. The present review exclusively discusses the demands to develop a novel eco-friendly management strategy to combat these global issues. This review also gives an intrinsic discussion about the insights of different aspects of environmental and public health concerns caused due to massive leachate generation, the abundance of antibiotics resistance (AR), and the effects of released leachate on the various environmental reservoirs and human health. Furthermore, the current review throws light on the source and fate of different ECs of landfill leachate and their possible impact on the nearby environments (groundwater, surface water, and soil) affecting human health. The present review strongly suggests the demand for future research focuses on the advancement of the removal efficiency of contaminants with the improvement of relevant landfill management to reduce the potential effects of disposable waste. We propose the necessity of the identification and monitoring of potential environmental and human health risks associated with landfill leachate contaminants.202133915892
658270.9901Effective Treatment Strategies for the Removal of Antibiotic-Resistant Bacteria, Antibiotic-Resistance Genes, and Antibiotic Residues in the Effluent From Wastewater Treatment Plants Receiving Municipal, Hospital, and Domestic Wastewater: Protocol for a Systematic Review. BACKGROUND: The widespread and unrestricted use of antibiotics has led to the emergence and spread of antibiotic-resistant bacteria (ARB), antibiotic-resistance genes (ARGs), and antibiotic residues in the environment. Conventional wastewater treatment plants (WWTPs) are not designed for effective and adequate removal of ARB, ARGs, and antibiotic residues, and therefore, they play an important role in the dissemination of antimicrobial resistance (AMR) in the natural environment. OBJECTIVE: We will conduct a systematic review to determine the most effective treatment strategies for the removal of ARB, ARGs, and antibiotic residues from the treated effluent disposed into the environment from WWTPs that receive municipal, hospital, and domestic discharge. METHODS: We will search the MEDLINE, EMBASE, Web of Science, World Health Organization Global Index Medicus, and ProQuest Environmental Science Collection databases for full-text peer-reviewed journal articles published between January 2001 and December 2020. We will select only articles published in the English language. We will include studies that measured (1) the presence, concentration, and removal rate of ARB/ARGs going from WWTP influent to effluent, (2) the presence, concentration, and types of antibiotics in the effluent, and (3) the possible selection of ARB in the effluent after undergoing treatment processes in WWTPs. At least two independent reviewers will extract data and perform risk of bias assessment. An acceptable or narrative synthesis method will be followed to synthesize the data and present descriptive characteristics of the included studies in a tabular form. The study has been approved by the Ethics Review Board at the International Centre for Diarrhoeal Disease Research, Bangladesh (protocol number: PR-20113). RESULTS: This protocol outlines our proposed methodology for conducting a systematic review. Our results will provide an update to the existing literature by searching additional databases. CONCLUSIONS: Findings from our systematic review will inform the planning of proper treatment methods that can effectively reduce the levels of ARB, ARGs, and residual antibiotics in effluent, thus lowering the risk of the environmental spread of AMR and its further transmission to humans and animals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33365.202134842550
665880.9901Antibiotic Resistant Superbugs: Assessment of the Interrelationship of Occurrence in Clinical Settings and Environmental Niches. The increasing threat to global health posed by antibiotic resistance remains of serious concern. Human health remains at higher risk due to several reported therapeutic failures to many life threatening drug resistant microbial infections. The resultant effects have been prolonged hospital stay, higher cost of alternative therapy, increased mortality, etc. This opinionated review considers the two main concerns in integrated human health risk assessment (i.e., residual antibiotics and antibiotic resistant genes) in various compartments of human environment, as well as clinical dynamics associated with the development and transfer of antibiotic resistance (AR). Contributions of quorum sensing, biofilms, enzyme production, and small colony variants in bacteria, among other factors in soil, water, animal farm and clinical settings were also considered. Every potential factor in environmental and clinical settings that brings about AR needs to be identified for the summative effects in overall resistance. There is a need to embrace coordinated multi-locational approaches and interrelationships to track the emergence of resistance in different niches in soil and water versus the hospital environment. The further integration with advocacy, legislation, enforcement, technological innovations and further research input and recourse to WHO guidelines on antibiotic policy would be advantageous towards addressing the emergence of antibiotic resistant superbugs.201628035988
713090.9901Microbial community structure and resistome dynamics on elevator buttons in response to surface disinfection practices. BACKGROUND: Disinfectants have been extensively used in public environments since the COVID-19 outbreak to help control the spread of the virus. This study aims to investigate whether disinfectant use influences the structure of bacterial communities and contributes to bacterial resistance to disinfectants and antibiotics. METHODS: Using molecular biology techniques-including metagenomic sequencing and quantitative PCR (qPCR)-we analyzed the bacterial communities on elevator button surfaces from two tertiary hospitals, one infectious disease hospital, two quarantine hotels (designated for COVID-19 control), and five general hotels in Nanjing, Jiangsu Province, during the COVID-19 pandemic. We focused on detecting disinfectant resistance genes (DRGs), antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs). RESULTS: Significant differences were observed in the bacterial community structures on elevator button surfaces across the four types of environments. Quarantine hotels, which implemented the most frequent disinfection protocols, exhibited distinct bacterial profiles at the phylum, genus, and species levels. Both α-diversity (within-sample diversity) and β-diversity (between-sample diversity) were lower and more distinct in quarantine hotels compared to the other environments. The abundance of DRGs, ARGs, and MGEs was also significantly higher on elevator button surfaces in quarantine hotels. Notably, antibiotic-resistant bacteria (ARBs), including Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa, were detected in all four settings. CONCLUSION: The structure of bacterial communities on elevator button surfaces varies across different environments, likely influenced by the frequency of disinfectant use. Increased resistance gene abundance in quarantine hotels suggests that disinfection practices may contribute to the selection and spread of resistant bacteria. Enhanced monitoring of disinfection effectiveness and refinement of protocols in high-risk environments such as hospitals and hotels are essential to limit the spread of resistant pathogens.202540520307
6646100.9900Food animals and antimicrobials: impacts on human health. Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the "precautionary principle." Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans-directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.201121976606
6472110.9900Balancing water sustainability and public health goals in the face of growing concerns about antibiotic resistance. Global initiatives are underway to advance the sustainability of urban water infrastructure through measures such as water reuse. However, there are growing concerns that wastewater effluents are enriched in antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes, and thus could serve as a contributing factor to growing rates of antibiotic resistance in human infections. Evidence for the role of the water environment as a source and pathway for the spread of antimicrobial resistance is examined and key knowledge gaps are identified with respect to implications for sustainable water systems. Efforts on the part of engineers along with investment in research in epidemiology, risk assessment, water treatment and water delivery could advance current and future sustainable water strategies and help avoid unintended consequences.201424279909
6407120.9900Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review. Urban wastewater treatment plants (UWTPs) are among the main sources of antibiotics' release into the environment. The occurrence of antibiotics may promote the selection of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB), which shade health risks to humans and animals. In this paper the fate of ARB and ARGs in UWTPs, focusing on different processes/technologies (i.e., biological processes, advanced treatment technologies and disinfection), was critically reviewed. The mechanisms by which biological processes influence the development/selection of ARB and ARGs transfer are still poorly understood. Advanced treatment technologies and disinfection process are regarded as a major tool to control the spread of ARB into the environment. In spite of intense efforts made over the last years to bring solutions to control antibiotic resistance spread in the environment, there are still important gaps to fill in. In particular, it is important to: (i) improve risk assessment studies in order to allow accurate estimates about the maximal abundance of ARB in UWTPs effluents that would not pose risks for human and environmental health; (ii) understand the factors and mechanisms that drive antibiotic resistance maintenance and selection in wastewater habitats. The final objective is to implement wastewater treatment technologies capable of assuring the production of UWTPs effluents with an acceptable level of ARB.201323396083
6395130.9899Risk control of antibiotics, antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB) during sewage sludge treatment and disposal: A review. Sewage sludge is an important reservoir of antibiotics, antibiotic resistance genes (ARGs), and antibiotic resistant bacteria (ARB) in wastewater treatment plants (WWTPs), and the reclamation of sewage sludge potentially threats human health and environmental safety. Sludge treatment and disposal are expected to control these risks, and this review summarizes the fate and controlling efficiency of antibiotics, ARGs, and ARB in sludge involved in different processes, i.e., disintegration, anaerobic digestion, aerobic composting, drying, pyrolysis, constructed wetland, and land application. Additionally, the analysis and characterization methods of antibiotics, ARGs, and ARB in complicate sludge are reviewed, and the quantitative risk assessment approaches involved in land application are comprehensively discussed. This review benefits process optimization of sludge treatment and disposal, with regard to environmental risks control of antibiotics, ARGs, and ARB in sludge. Furthermore, current research limitations and gaps, e.g., the antibiotic resistance risk assessment in sludge-amended soil, are proposed to advance the future studies.202336933744
6508140.9899Synergizing Ecotoxicology and Microbiome Data Is Key for Developing Global Indicators of Environmental Antimicrobial Resistance. The One Health concept recognises the interconnectedness of humans, plants, animals and the environment. Recent research strongly supports the idea that the environment serves as a significant reservoir for antimicrobial resistance (AMR). However, the complexity of natural environments makes efforts at AMR public health risk assessment difficult. We lack sufficient data on key ecological parameters that influence AMR, as well as the primary proxies necessary for evaluating risks to human health. Developing environmental AMR 'early warning systems' requires models with well-defined parameters. This is necessary to support the implementation of clear and targeted interventions. In this review, we provide a comprehensive overview of the current tools used globally for environmental AMR human health risk assessment and the underlying knowledge gaps. We highlight the urgent need for standardised, cost-effective risk assessment frameworks that are adaptable across different environments and regions to enhance comparability and reliability. These frameworks must also account for previously understudied AMR sources, such as horticulture, and emerging threats like climate change. In addition, integrating traditional ecotoxicology with modern 'omics' approaches will be essential for developing more comprehensive risk models and informing targeted AMR mitigation strategies.202439611949
6418150.9899Antibiotic resistance genes in anaerobic digestion: Unresolved challenges and potential solutions. Antimicrobial resistance (AMR) threatens public health, necessitating urgent efforts to mitigate the global impact of antibiotic resistance genes (ARGs). Anaerobic digestion (AD), known for volatile solid reduction and energy generation, also presents a feasible approach for the removal of ARGs. This review encapsulates the existing understanding of ARGs and antibiotic-resistant bacteria (ARB) during the AD process, highlighting unresolved challenges pertaining to their detection and quantification. The questions raised and discussed include: Do current ARGs detection methods meet qualitative and quantitative requirements? How can we conduct risk assessments of ARGs? What happens to ARGs when they come into co-exposure with other emerging pollutants? How can the application of internal standards bolster the reliability of the AD resistome study? What are the potential future research directions that could enhance ARG elimination? Investigating these subjects will assist in shaping more efficient management strategies that employ AD for effective ARG control.202539826759
6423160.9899Emerging soil contamination of antibiotics resistance bacteria (ARB) carrying genes (ARGs): New challenges for soil remediation and conservation. Soil plays a vital role as a nutrient source for microflora and plants in ecosystems. The accumulation and proliferation of antibiotics resistance bacteria (ARB) and antibiotics resistance genes (ARGs) causes emerging soil contamination and pollution, posing new challenges for soil remediation, recovery, and conservation. Fertilizer application in agriculture is one of the most important sources of ARB and ARGs contamination in soils. The recent existing techniques for the remediation of soil polluted with ARB and ARGs are very limited in terms of ARB and ARGs removal in soil. Bioelectrochemical remediation using bioelectrochemical systems such as microbial fuel cells and microbial electrolysis cells are promising technologies for the removal of ARB and ARGs in soil. Herein, diverse sources of ARB and ARGs in soil have been reviewed, their effects on soil microbial diversity have been analyzed, and the causes of ARB and ARGs rapid proliferation in soil are explained. Bioelectrochemical systems used for the remediation of soil contaminated with ARB and ARGs is still in its infancy stage and presents serious disadvantage and limits, therefore it needs to be well understood and implemented. In general, merging soil contamination of ARB and ARGs is an increasing concern threatening the soil ecosystem while the remediation technologies are still challenging. Efforts need to be made to develop new, effective, and efficient technologies for soil remediation and conservation to tackle the spread of ARB and ARGs and overcome the new challenges posed by ARB and ARGs contamination in soil.202336563979
6470170.9899The urgent need for risk assessment on the antibiotic resistance spread via sewage sludge land application. Sewage sludge is an ever-increasing by-product of the wastewater treatment process frequently used as a soil fertiliser. To control its quality and prevent any possible hazardous impact of fertilisation, some mandatory limits of heavy metal content have been established by the European Commission (Sewage Sludge Directive). However, since the implementation of the limits, new emerging contaminants have been reported worldwide. Regardless of the wastewater treatment process, sewage sludge contains antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes, which can be released into the environment through its land application. Such a practice may even boost the dissemination and further development of antibiotic resistance phenomenon - already a global problem challenging modern medicine. Due to the growing pharmaceutical pollution in the environment, the time is ripe to assess the risk for the human and environmental health of sewage sludge land application in the context of antibiotic resistance spread. In this review we present the current knowledge in the field and we emphasise the necessity for more studies.201626646979
6714180.9899Differential Drivers of Antimicrobial Resistance across the World. Antimicrobial resistance (AMR) is one of the greatest threats faced by humankind. The development of resistance in clinical and hospital settings has been well documented ever since the initial discovery of penicillin and the subsequent introduction of sulfonamides as clinical antibiotics. In contrast, the environmental (i.e., community-acquired) dimensions of resistance dissemination have been only more recently delineated. The global spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) between air, water, soil, and food is now well documented, while the factors that affect ARB and ARG dissemination (e.g., water and air quality, antibiotic fluxes, urbanization, sanitation practices) in these and other environmental matrices are just now beginning to be more fully appreciated. In this Account, we discuss how the global perpetuation of resistance is dictated by highly interconnected socioeconomic risk factors and illustrate that development status should be more fully considered when developing global strategies to address AMR. We first differentiate low to middle income countries (LMICs) and high-income countries (HICs), then we summarize the modes of action of commercially available antibiotics, and then discuss the four primary mechanisms by which bacteria develop resistance to those antibiotics. Resistance is disseminated via both vertical gene transfer (VGT; parent to offspring) as well as by horizontal gene transfer (HGT; cell to cell transference of genetic material). A key challenge hindering attempts to control resistance dissemination is the presence of native, environmental bacteria that can harbor ARGs. Such environmental "resistomes" have potential to transfer resistance to pathogens via HGT. Of particular concern is the development of resistance to antibiotics of last-resort such as the cephalosporins, carbapenems, and polymyxins. We then illustrate how antibiotic use differs in LMICs relative to HICs in terms of the volumes of antibiotics used and their fate within local environments. Antibiotic use in HICs has remained flat over the past 15 years, while in LMICs use over the same period has increased substantially as a result of economic improvements and changes in diet. These use and fate differences impact local citizens and thus the local dissemination of AMR. Various physical, social, and economic circumstances within LMICs potentially favor AMR dissemination. We focus on three physical factors: changing population density, sanitation infrastructure, and solid-waste disposal. We show that high population densities in cities within LMICs that suffer from poor sanitation and solid-waste disposal can potentially impact the dissemination of resistance. In the final section, we discuss potential monitoring approaches to quantify the spread of resistance both within LMICs as well as in HICs. We posit that culture-based approaches, molecular approaches, and cutting-edge nanotechnology-based methods for monitoring ARB and ARGs should be considered both within HICs and, as appropriate, within LMICs.201930848890
6716190.9899Wastewater surveillance of antibiotic-resistant bacteria for public health action: potential and challenges. Antibiotic resistance is an urgent public health threat. Actions to reduce this threat include requiring prescriptions for antibiotic use, antibiotic stewardship programs, educational programs targeting patients and healthcare providers, and limiting antibiotic use in agriculture, aquaculture, and animal husbandry. Wastewater surveillance might complement clinical surveillance by tracking time/space variation essential for detecting outbreaks and evaluating efficacy of evidence-based interventions, identifying high-risk populations for targeted monitoring, providing early warning of the emergence and spread of antibiotic-resistant bacteria (ARBs), and identifying novel antibiotic-resistant threats. Wastewater surveillance was an effective early warning system for SARS-CoV-2 spread and detection of the emergence of new viral strains. In this data-driven commentary, we explore whether monitoring wastewater for antibiotic-resistant genes (ARGs) and/or bacteria resistant to antibiotics might provide useful information for public health action. Using carbapenem resistance as an example, we highlight technical challenges associated with using wastewater to quantify temporal/spatial trends in ARBs and ARGs and compare with clinical information. While ARGs and ARBs are detectable in wastewater enabling early detection of novel ARGs, quantitation of ARBs and ARGs with current methods is too variable to reliably track space/time variation.202539475072