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668600.9933The 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
650610.9930Mitigating 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
664920.9930 The development of antibiotics has provided much success against infectious diseases in animals and humans. But the intensive and extensive use of antibiotics over the years has resulted in the emergence of drug-resistant bacterial pathogens. The existence of a reservoir(s) of antibiotic resistant bacteria and antibiotic resistance genes in an interactive environment of animals, plants, and humans provides the opportunity for further transfer and dissemination of antibiotic resistance. The emergence of antibiotic resistant bacteria has created growing concern about its impact on animal and human health. To specifically address the impact of antibiotic resistance resulting from the use of antibiotics in agriculture, the American Academy of Microbiology convened a colloquium, “Antibiotic Resistance and the Role of Antimicrobials in Agriculture: A Critical Scientific Assessment,” in Santa Fe, New Mexico, November 2–4, 2001. Colloquium participants included academic, industrial, and government researchers with a wide range of expertise, including veterinary medicine, microbiology, food science, pharmacology, and ecology. These scientists were asked to provide their expert opinions on the current status of antibiotic usage and antibiotic resistance, current research information, and provide recommendations for future research needs. The research areas to be addressed were roughly categorized under the following areas: ▪ Origins and reservoirs of resistance; ▪ Transfer of resistance; ▪ Overcoming/modulating resistance by altering usage; and ▪ Interrupting transfer of resistance. The consensus of colloquium participants was that the evaluation of antibiotic usage and its impact were complex and subject to much speculation and polarization. Part of the complexity stems from the diverse array of animals and production practices for food animal production. The overwhelming consensus was that any use of antibiotics creates the possibility for the development of antibiotic resistance, and that there already exist pools of antibiotic resistance genes and antibiotic resistant bacteria. Much discussion revolved around the measurement of antibiotic usage, the measurement of antibiotic resistance, and the ability to evaluate the impact of various types of usage (animal, human) on overall antibiotic resistance. Additionally, many participants identified commensal bacteria as having a possible role in the continuance of antibiotic resistance as reservoirs. Participants agreed that many of the research questions could not be answered completely because of their complexity and the need for better technologies. The concept of the “smoking gun” to indicate that a specific animal source was important in the emergence of certain antibiotic resistant pathogens was discussed, and it was agreed that ascribing ultimate responsibility is likely to be impossible. There was agreement that expanded and more improved surveillance would add to current knowledge. Science-based risk assessments would provide better direction in the future. As far as preventive or intervention activities, colloquium participants reiterated the need for judicious/prudent use guidelines. Yet they also emphasized the need for better dissemination and incorporation by end-users. It is essential that there are studies to measure the impact of educational efforts on antibiotic usage. Other recommendations included alternatives to antibiotics, such as commonly mentioned vaccines and probiotics. There also was an emphasis on management or production practices that might decrease the need for antibiotics. Participants also stressed the need to train new researchers and to interest students in postdoctoral work, through training grants, periodic workshops, and comprehensive conferences. This would provide the expertise needed to address these difficult issues in the future. Finally, the participants noted that scientific societies and professional organizations should play a pivotal role in providing technical advice, distilling and disseminating information to scientists, media, and consumers, and in increasing the visibility and funding for these important issues. The overall conclusion is that antibiotic resistance remains a complex issue with no simple answers. This reinforces the messages from other meetings. The recommendations from this colloquium provide some insightful directions for future research and action.200232687288
666430.9930Addressing the global challenge of bacterial drug resistance: insights, strategies, and future directions. The COVID-19 pandemic underscored bacterial resistance as a critical global health issue, exacerbated by the increased use of antibiotics during the crisis. Notwithstanding the pandemic's prevalence, initiatives to address bacterial medication resistance have been inadequate. Although an overall drop in worldwide antibiotic consumption, total usage remains substantial, requiring rigorous regulatory measures and preventive activities to mitigate the emergence of resistance. Although National Action Plans (NAPs) have been implemented worldwide, significant disparities persist, particularly in low- and middle-income countries (LMICs). Settings such as farms, hospitals, wastewater treatment facilities, and agricultural environments include a significant presence of Antibiotic Resistant Bacteria (ARB) and antibiotic-resistance genes (ARG), promoting the propagation of resistance. Dietary modifications and probiotic supplementation have shown potential in reshaping gut microbiota and reducing antibiotic resistance gene prevalence. Combining antibiotics with adjuvants or bacteriophages may enhance treatment efficacy and mitigate resistance development. Novel therapeutic approaches, such as tailored antibiotics, monoclonal antibodies, vaccines, and nanoparticles, offer alternate ways of addressing resistance. In spite of advancements in next-generation sequencing and analytics, gaps persist in comprehending the role of gut microbiota in regulating antibiotic resistance. Effectively tackling antibiotic resistance requires robust policy interventions and regulatory measures targeting root causes while minimizing public health risks. This review provides information for developing strategies and protocols to prevent bacterial colonization, enhance gut microbiome resilience, and mitigate the spread of antibiotic resistance.202540066274
908340.9930ARGNet: 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
668950.9930Wastewater-Based Epidemiology as a Complementary Tool for Antimicrobial Resistance Surveillance: Overcoming Barriers to Integration. This commentary highlights the potential of wastewater-based epidemiology (WBE) as a complementary tool for antimicrobial resistance (AMR) surveillance. WBE can support the early detection of resistance trends at the population level, including in underserved communities. However, several challenges remain, including technical variability, complexities in data interpretation, and regulatory gaps. An additional limitation is the uncertainty surrounding the origin of resistant bacteria and their genes in wastewater, which may derive not only from human sources but also from industrial, agricultural, or infrastructural contributors. Therefore, effective integration of WBE into public health systems will require standardized methods, sustained investment, and cross-sector collaboration. This could be achieved through joint monitoring initiatives that combine hospital wastewater data with agricultural and municipal surveillance to inform antibiotic stewardship policies. Overcoming these barriers could position WBE as an innovative tool for AMR monitoring, enhancing early warning systems and supporting more responsive, equitable, and preventive public health strategies.202540522150
907560.9929CamPype: an open-source workflow for automated bacterial whole-genome sequencing analysis focused on Campylobacter. BACKGROUND: The rapid expansion of Whole-Genome Sequencing has revolutionized the fields of clinical and food microbiology. However, its implementation as a routine laboratory technique remains challenging due to the growth of data at a faster rate than can be effectively analyzed and critical gaps in bioinformatics knowledge. RESULTS: To address both issues, CamPype was developed as a new bioinformatics workflow for the genomics analysis of sequencing data of bacteria, especially Campylobacter, which is the main cause of gastroenteritis worldwide making a negative impact on the economy of the public health systems. CamPype allows fully customization of stages to run and tools to use, including read quality control filtering, read contamination, reads extension and assembly, bacterial typing, genome annotation, searching for antibiotic resistance genes, virulence genes and plasmids, pangenome construction and identification of nucleotide variants. All results are processed and resumed in an interactive HTML report for best data visualization and interpretation. CONCLUSIONS: The minimal user intervention of CamPype makes of this workflow an attractive resource for microbiology laboratories with no expertise in bioinformatics as a first line method for bacterial typing and epidemiological analyses, that would help to reduce the costs of disease outbreaks, or for comparative genomic analyses. CamPype is publicly available at https://github.com/JoseBarbero/CamPype .202337474912
664870.9929Multi-Drug Resistant Coliform: Water Sanitary Standards and Health Hazards. Water constitutes and sustains life; however, its pollution afflicts its necessity, further worsening its scarcity. Coliform is one of the largest groups of bacteria evident in fecally polluted water, a major public health concern. Coliform thrive as commensals in the gut of warm-blooded animals, and are indefinitely passed through their feces into the environment. They are also called as model organisms as their presence is indicative of the prevalence of other potential pathogens, thus coliform are and unanimously employed as adept indicators of fecal pollution. As only a limited accessible source of fresh water is available on the planet, its contamination severely affects its usability. Coliform densities vary geographically and seasonally which leads to the lack of universally uniform regulatory guidelines regarding water potability often leads to ineffective detection of these model organisms and the misinterpretation of water quality status. Remedial measures such as disinfection, reducing the nutrient concentration or re-population doesn't hold context in huge lotic ecosystems such as freshwater rivers. There is also an escalating concern regarding the prevalence of multi-drug resistance in coliforms which renders antibiotic therapy incompetent. Antimicrobials are increasingly used in household, clinical, veterinary, animal husbandry and agricultural settings. Sub-optimal concentrations of these antimicrobials are unintentionally but regularly dispensed into the environment through seepages, sewages or runoffs from clinical or agricultural settings substantially adding to the ever-increasing pool of antibiotic resistance genes. When present below their minimum inhibitory concentration (MIC), these antimicrobials trigger the transfer of antibiotic-resistant genes that the coliform readily assimilate and further propagate to pathogens, the severity of which is evidenced by the high Multiple Antibiotic Resistance (MAR) index shown by the bacterial isolates procured from the environmental. This review attempts to assiduously anthologize the use of coliforms as water quality standards, their existent methods of detection and the issue of arising multi-drug resistance in them.201829946253
665080.9928 Antibiotic resistance is never going to go away. No matter how many drugs we throw at it, no matter how much money and resources are sacrificed to wage a war on resistance, it will always prevail. Humans are forced to coexist with the fact of antibiotic resistance. Public health officials, clinicians, and scientists must find effective ways to cope with antibiotic resistant bacteria harmful to humans and animals and to control the development of new types of resistance. The American Academy of Microbiology convened a colloquium October 12–14, 2008, to discuss antibiotic resistance and the factors that influence the development and spread of resistance. Participants, whose areas of expertise included medicine, microbiology, and public health, made specific recommendations for needed research, policy development, a surveillance network, and treatment guidelines. Antibiotic resistance issues specific to the developing world were discussed and recommendations for improvements were made. Each antibiotic is injurious only to a certain segment of the microbial world, so for a given antibacterial there are some species of bacteria that are susceptible and others not. Bacterial species insusceptible to a particular drug are “naturally resistant.” Species that were once sensitive but eventually became resistant to it are said to have “acquired resistance.” It is important to note that “acquired resistance” affects a subset of strains in the entire species; that is why the prevalence of “acquired resistance” in a species is different according to location. Antibiotic resistance, the acquired ability of a pathogen to withstand an antibiotic that kills off its sensitive counterparts, originally arises from random mutations in existing genes or from intact genes that already serve a similar purpose. Exposure to antibiotics and other antimicrobial products, whether in the human body, in animals, or the environment, applies selective pressure that encourages resistance to emerge favoring both “naturally resistant” strains and strains which have “acquired resistance.” Horizontal gene transfer, in which genetic information is passed between microbes, allows resistance determinants to spread within harmless environmental or commensal microorganisms and pathogens, thus creating a reservoir of resistance. Resistance is also spread by the replication of microbes that carry resistance genes, a process that produces genetically identical (or clonal) progeny. Rapid diagnostic methods and surveillance are some of the most valuable tools in preventing the spread of resistance. Access to more rapid diagnostic tests that could determine the causative agent and antibiotic susceptibility of infections would inform better decision making with respect to antibiotic use, help slow the selection of resistant strains in clinical settings, and enable better disease surveillance. A rigorous surveillance network to track the evolution and spread of resistance is also needed and would probably result in significant savings in healthcare. Developing countries face unique challenges when it comes to antibiotic resistance; chief among them may be the wide availability of antibiotics without a prescription and also counterfeit products of dubious quality. Lack of adequate hygiene, poor water quality, and failure to manage human waste also top the list. Recommendations for addressing the problems of widespread resistance in the developing world include: proposals for training and infrastructure capacity building; surveillance programs; greater access to susceptibility testing; government controls on import, manufacture and use; development and use of vaccines; and incentives for pharmaceutical companies to supply drugs to these countries. Controlling antibiotic resistant bacteria and subsequent infections more efficiently necessitates the prudent and responsible use of antibiotics. It is mandatory to prevent the needless use of antibiotics (e.g., viral infections; unnecessary prolonged treatment) and to improve the rapid prescription of appropriate antibiotics to a patient. Delayed or inadequate prescriptions reduce the efficacy of treatment and favor the spread of the infection. Prudent use also applies to veterinary medicine. For example, antibiotics used as “growth promoters” have been banned in Europe and are subject to review in some other countries. There are proven techniques for limiting the spread of resistance, including hand hygiene, but more rapid screening techniques are needed in order to effectively track and prevent spread in clinical settings. The spread of antibiotic resistance on farms and in veterinary hospitals may also be significant and should not be neglected. Research is needed to pursue alternative approaches, including vaccines, antisense therapy, public health initiatives, and others. The important messages about antibiotic resistance are not getting across from scientists and infectious diseases specialists to prescribers, stakeholders, including the public, healthcare providers, and public officials. Innovative and effective communication initiatives are needed, as are carefully tailored messages for each of the stakeholder groups.200932644325
259990.9927Evaluation of whole-genome sequencing protocols for detection of antimicrobial resistance, virulence factors and mobile genetic elements in antimicrobial-resistant bacteria. Introduction. Antimicrobial resistance (AMR) poses a critical threat to global health, underscoring the need for rapid and accurate diagnostic tools. Methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL-Kp) are listed among the World Health Organization's priority pathogens.Hypothesis. A rapid nanopore-based protocol can accurately and efficiently detect AMR genes, virulence factors (VFs) and mobile genetic elements (MGEs) in MRSA and ESBL-Kp, offering performance comparable to or superior to traditional sequencing methods.Aim. Evaluate whole-genome sequencing (WGS) protocols for detecting AMR genes, VFs and MGEs in MRSA and ESBL-Kp, to identify the most accurate and efficient tool for pathogen profiling.Methodology. Five distinct WGS protocols, including a rapid nanopore-based protocol (ONT20h) and four slower sequencing methods, were evaluated for their effectiveness in detecting genetic markers. The protocols' performances were compared across AMR genes, VFs and MGEs. Additionally, phenotypic antimicrobial susceptibility testing was performed to assess concordance with the genomic findings.Results. Compared to four slower sequencing protocols, the rapid nanopore-based protocol (ONT20h) demonstrated comparable or superior performance in AMR gene detection and equivalent VF identification. Although MGE detection varied among protocols, ONT20h showed a high level of agreement with phenotypic antimicrobial susceptibility testing.Conclusion. The findings highlight the potential of rapid WGS as a valuable tool for clinical microbiology, enabling timely implementation of infection control measures and informed therapeutic decisions. However, further studies are required to optimize the clinical application of this technology, considering costs, availability of bioinformatics tools and quality of reference databases.202540105741
2525100.9927Review of antimicrobial resistance surveillance programmes in livestock and meat in EU with focus on humans. OBJECTIVES: In this review, we describe surveillance programmes reporting antimicrobial resistance (AMR) and resistance genes in bacterial isolates from livestock and meat and compare them with those relevant for human health. METHODS: Publications on AMR in European countries were assessed. PubMed was reviewed and AMR monitoring programmes were identified from reports retrieved by Internet searches and by contacting national authorities in EU/European Economic Area (EEA) member states. RESULTS: Three types of systems were identified: EU programmes, industry-funded supranational programmes and national surveillance systems. The mandatory EU-financed programme has led to some harmonization in national monitoring and provides relevant information on AMR and extended-spectrum β-lactamase/AmpC- and carbapenemase-producing bacteria. At the national level, AMR surveillance systems in livestock apply heterogeneous sampling, testing and reporting modalities, resulting in results that cannot be compared. Most reports are not publicly available or are written in a local language. The industry-funded monitoring systems undertaken by the Centre Européen d'Etudes pour la Santé Animale (CEESA) examines AMR in bacteria in food-producing animals. CONCLUSIONS: Characterization of AMR genes in livestock is applied heterogeneously among countries. Most antibiotics of human interest are included in animal surveillance, although results are difficult to compare as a result of lack of representativeness of animal samples. We suggest that EU/EEA countries provide better uniform AMR monitoring and reporting in livestock and link them better to surveillance systems in humans. Reducing the delay between data collection and publication is also important to allow prompt identification of new resistance patterns.201828970159
6582110.9927Effective 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
6691120.9927The antimicrobial resistance monitoring and research (ARMoR) program: the US Department of Defense response to escalating antimicrobial resistance. Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration, the Antimicrobial Resistance Monitoring and Research Program, to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, bacteria containing AMR-encoding genes are increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program.201424795331
6657130.9927From Cure to Crisis: Understanding the Evolution of Antibiotic-Resistant Bacteria in Human Microbiota. The growing prevalence of antibiotic-resistant bacteria within the human microbiome has become a pressing global health crisis. While antibiotics have revolutionized medicine by significantly reducing mortality and enabling advanced medical interventions, their misuse and overuse have led to the emergence of resistant bacterial strains. Key resistance mechanisms include genetic mutations, horizontal gene transfer, and biofilm formation, with the human microbiota acting as a reservoir for antibiotic resistance genes (ARGs). Industrialization and environmental factors have exacerbated this issue, contributing to a rise in infections with multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae. These resistant pathogens compromise the effectiveness of essential treatments like surgical prophylaxis and chemotherapy, increase healthcare costs, and prolong hospital stays. This crisis highlights the need for a global One-Health approach, particularly in regions with weak regulatory frameworks. Innovative strategies, including next-generation sequencing (NGS) technologies, offer promising avenues for mitigating resistance. Addressing this challenge requires coordinated efforts, encompassing research, policymaking, public education, and antibiotic stewardship, to safeguard current antibiotics and foster the development of new therapeutic solutions. An integrated, multidimensional strategy is essential to tackle this escalating problem and ensure the sustainability of effective antimicrobial treatments.202539858487
6718140.9927Agroecosystem exploration for Antimicrobial Resistance in Ahmedabad, India: A Study Protocol. INTRODUCTION: Antimicrobial resistance (AMR) has emerged as one of the leading threats to public health. AMR possesses a multidimensional challenge that has social, economic, and environmental dimensions that encompass the food production system, influencing human and animal health. The One Health approach highlights the inextricable linkage and interdependence between the health of people, animal, agriculture, and the environment. Antibiotic use in any of these areas can potentially impact the health of others. There is a dearth of evidence on AMR from the natural environment, such as the plant-based agriculture sector. Antibiotics, antibiotic-resistant bacteria (ARB), and related AMR genes (ARGs) are assumed to present in the natural environment and disseminate resistance to fresh produce/vegetables and thus to human health upon consumption. Therefore, this study aims to investigate the role of vegetables in the spread of AMR through an agroecosystem exploration in Ahmedabad, India. PROTOCOL: The present study will be executed in Ahmedabad, located in Gujarat state in the Western part of India, by adopting a mixed-method approach. First, a systematic review will be conducted to document the prevalence of ARB and ARGs on fresh produce in South Asia. Second, agriculture farmland surveys will be used to collect the general farming practices and the data on common vegetables consumed raw by the households in Ahmedabad. Third, vegetable and soil samples will be collected from the selected agriculture farms and analyzed for the presence or absence of ARB and ARGs using standard microbiological and molecular methods. DISCUSSION: The analysis will help to understand the spread of ARB/ARGs through the agroecosystem. This is anticipated to provide an insight into the current state of ARB/ARGs contamination of fresh produce/vegetables and will assist in identifying the relevant strategies for effectively controlling and preventing the spread of AMR.202338644926
5115150.9926Search Engine for Antimicrobial Resistance: A Cloud Compatible Pipeline and Web Interface for Rapidly Detecting Antimicrobial Resistance Genes Directly from Sequence Data. BACKGROUND: Antimicrobial resistance remains a growing and significant concern in human and veterinary medicine. Current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria are limited in their effectiveness and scope. With the rapidly developing field of whole genome sequencing beginning to be utilised in clinical practice, the ability to interrogate sequencing data quickly and easily for the presence of antimicrobial resistance genes will become increasingly important and useful for informing clinical decisions. Additionally, use of such tools will provide insight into the dynamics of antimicrobial resistance genes in metagenomic samples such as those used in environmental monitoring. RESULTS: Here we present the Search Engine for Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of horizontally acquired antimicrobial resistance genes in raw sequencing data. The pipeline provides gene information, abundance estimation and the reconstructed sequence of antimicrobial resistance genes; it also provides web links to additional information on each gene. The pipeline utilises clustering and read mapping to annotate full-length genes relative to a user-defined database. It also uses local alignment of annotated genes to a range of online databases to provide additional information. We demonstrate SEAR's application in the detection and abundance estimation of antimicrobial resistance genes in two novel environmental metagenomes, 32 human faecal microbiome datasets and 126 clinical isolates of Shigella sonnei. CONCLUSIONS: We have developed a pipeline that contributes to the improved capacity for antimicrobial resistance detection afforded by next generation sequencing technologies, allowing for rapid detection of antimicrobial resistance genes directly from sequencing data. SEAR uses raw sequencing data via an intuitive interface so can be run rapidly without requiring advanced bioinformatic skills or resources. Finally, we show that SEAR is effective in detecting antimicrobial resistance genes in metagenomic and isolate sequencing data from both environmental metagenomes and sequencing data from clinical isolates.201526197475
5098160.9926Feature selection and aggregation for antibiotic resistance GWAS in Mycobacterium tuberculosis: a comparative study. INTRODUCTION: Drug resistance (DR) of pathogens remains a global healthcare concern. In contrast to other bacteria, acquiring mutations in the core genome is the main mechanism of drug resistance for Mycobacterium tuberculosis (MTB). For some antibiotics, the resistance of a particular isolate can be reliably predicted by identifying specific mutations, while for other antibiotics the knowledge of resistance mechanisms is limited. Statistical machine learning (ML) methods are used to infer new genes implicated in drug resistance leveraging large collections of isolates with known whole-genome sequences and phenotypic states for different drugs. However, high correlations between the phenotypic states for commonly used drugs complicate the inference of true associations of mutations with drug phenotypes by ML approaches. METHODS: Recently, several new methods have been developed to select a small subset of reliable predictors of the dependent variable, which may help reduce the number of spurious associations identified. In this study, we evaluated several such methods, namely, logistic regression with different regularization penalty functions, a recently introduced algorithm for solving the best-subset selection problem (ABESS) and "Hungry, Hungry SNPos" (HHS) a heuristic algorithm specifically developed to identify resistance-associated genetic variants in the presence of resistance co-occurrence. We assessed their ability to select known causal mutations for resistance to a specific drug while avoiding the selection of mutations in genes associated with resistance to other drugs, thus we compared selected ML models for their applicability for MTB genome wide association studies. RESULTS AND DISCUSSION: In our analysis, ABESS significantly outperformed the other methods, selecting more relevant sets of mutations. Additionally, we demonstrated that aggregating rare mutations within protein-coding genes into markers indicative of changes in PFAM domains improved prediction quality, and these markers were predominantly selected by ABESS, suggesting their high informativeness. However, ABESS yielded lower prediction accuracy compared to logistic regression methods with regularization.202540606161
6507170.9926What Are the Drivers Triggering Antimicrobial Resistance Emergence and Spread? Outlook from a One Health Perspective. Antimicrobial resistance (AMR) has emerged as a critical global public health threat, exacerbating healthcare burdens and imposing substantial economic costs. Currently, AMR contributes to nearly five million deaths annually worldwide, surpassing mortality rates of any single infectious disease. The economic burden associated with AMR-related disease management is estimated at approximately $730 billion per year. This review synthesizes current research on the mechanisms and multifaceted drivers of AMR development and dissemination through the lens of the One Health framework, which integrates human, animal, and environmental health perspectives. Intrinsic factors, including antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs), enable bacteria to evolve adaptive resistance mechanisms such as enzymatic inactivation, efflux pumps, and biofilm formation. Extrinsic drivers span environmental stressors (e.g., antimicrobials, heavy metals, disinfectants), socioeconomic practices, healthcare policies, and climate change, collectively accelerating AMR proliferation. Horizontal gene transfer and ecological pressures further facilitate the spread of antimicrobial-resistant bacteria across ecosystems. The cascading impacts of AMR threaten human health and agricultural productivity, elevate foodborne infection risks, and impose substantial economic burdens, particularly in low- and middle-income countries. To address this complex issue, the review advocates for interdisciplinary collaboration, robust policy implementation (e.g., antimicrobial stewardship), and innovative technologies (e.g., genomic surveillance, predictive modeling) under the One Health paradigm. Such integrated strategies are essential to mitigate AMR transmission, safeguard global health, and ensure sustainable development.202540558133
6581180.9926Do wastewater treatment plants increase antibiotic resistant bacteria or genes in the environment? Protocol for a systematic review. BACKGROUND: Antibiotic resistance is a global public health threat. Water from human activities is collected at wastewater treatment plants where processes often do not sufficiently neutralize antibiotic resistant bacteria and genes, which are further shed into the local environment. This protocol outlines the steps to conduct a systematic review based on the Population, Exposure, Comparator and Outcome (PECO) framework, aiming at answering the question "Are antimicrobial-resistant enterobacteriaceae and antimicrobial resistance genes present (O) in air and water samples (P) taken either near or downstream or downwind or down-gradient from wastewater treatment plants (E), as compared to air and water samples taken either further away or upstream or upwind or up-gradient from such wastewater treatment plant (C)?" Presence of antimicrobial-resistant bacteria and genes will be quantitatively measured by extracting their prevalence or concentration, depending on the reviewed study. METHODS: We will search PubMed, EMBASE, the Cochrane database and Web of Science for original articles published from 1 Jan 2000 to 3 Sep 2018 with language restriction. Articles will undergo a relevance and a design screening process. Data from eligible articles will be extracted by two independent reviewers. Further, we will perform a risk of bias assessment using a decision matrix. We will synthesize and present results in narrative and tabular form and will perform a meta-analysis if heterogeneity of results allows it. DISCUSSION: Antibiotic resistance in environmental samples around wastewater treatment plants may pose a risk of exposure to workers and nearby residents. Results from the systematic review outlined in this protocol will allow to estimate the extend of exposure, to inform policy making and help to design future studies.201931806019
4886190.9926Molecular diagnostics for genotypic detection of antibiotic resistance: current landscape and future directions. Antimicrobial resistance (AMR) among bacteria is an escalating public health emergency that has worsened during the COVID-19 pandemic. When making antibiotic treatment decisions, clinicians rely heavily on determination of antibiotic susceptibility or resistance by the microbiology laboratory, but conventional methods often take several days to identify AMR. There are now several commercially available molecular methods that detect antibiotic resistance genes within hours rather than days. While these methods have limitations, they offer promise for optimizing treatment and patient outcomes, and reducing further emergence of AMR. This review provides an overview of commercially available genotypic assays that detect individual resistance genes and/or resistance-associated mutations in a variety of specimen types and discusses how clinical outcomes studies may be used to demonstrate clinical utility of such diagnostics.202336816746