# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8161 | 0 | 0.9914 | Integrative strategies against multidrug-resistant bacteria: Synthesizing novel antimicrobial frontiers for global health. Concerningly, multidrug-resistant bacteria have emerged as a prime worldwide trouble, obstructing the treatment of infectious diseases and causing doubts about the therapeutic accidentalness of presently existing drugs. Novel antimicrobial interventions deserve development as conventional antibiotics are incapable of keeping pace with bacteria evolution. Various promising approaches to combat MDR infections are discussed in this review. Antimicrobial peptides are examined for their broad-spectrum efficacy and reduced ability to develop resistance, while phage therapy may be used under extreme situations when antibiotics fail. In addition, the possibility of CRISPR-Cas systems for specifically targeting and eradicating resistance genes from bacterial populations will be explored. Nanotechnology has opened up the route to improve the delivery system of the drug itself, increasing the efficacy and specificity of antimicrobial action while protecting its host. Discovering potential antimicrobial agents is an exciting prospect through developments in synthetic biology and the rediscovery of natural product-based medicines. Moreover, host-directed therapies are now becoming popular as an adjunct to the main strategies of therapeutics without specifically targeting pathogens. Although these developments appear impressive, questions about production scaling, regulatory approvals, safety, and efficacy for clinical employment still loom large. Thus, tackling the MDR burden requires a multi-pronged plan, integrating newer treatment modalities with existing antibiotic regimens, enforcing robust stewardship initiatives, and effecting policy changes at the global level. The international health community can gird itself against the growing menace of antibiotic resistance if collaboration between interdisciplinary bodies and sustained research endeavours is encouraged. In this study, we evaluate the synergistic potential of combining various medicines in addition to summarizing recent advancements. To rethink antimicrobial stewardship in the future, we provide a multi-tiered paradigm that combines pathogen-focused and host-directed strategies. | 2025 | 40914328 |
| 6649 | 1 | 0.9913 | 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. | 2002 | 32687288 |
| 6650 | 2 | 0.9912 | 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. | 2009 | 32644325 |
| 5103 | 3 | 0.9908 | Revolutionising bacteriology to improve treatment outcomes and antibiotic stewardship. LABORATORY INVESTIGATION OF BACTERIAL INFECTIONS GENERALLY TAKES TWO DAYS: one to grow the bacteria and another to identify them and to test their susceptibility. Meanwhile the patient is treated empirically, based on likely pathogens and local resistance rates. Many patients are over-treated to prevent under-treatment of a few, compromising antibiotic stewardship. Molecular diagnostics have potential to improve this situation by accelerating precise diagnoses and the early refinement of antibiotic therapy. They include: (i) the use of 'biomarkers' to swiftly distinguish patients with bacterial infection, and (ii) molecular bacteriology to identify pathogens and their resistance genes in clinical specimens, without culture. Biomarker interest centres on procalcitonin, which has given good results particularly for pneumonias, though broader biomarker arrays may prove superior in the future. PCRs already are widely used to diagnose a few infections (e.g. tuberculosis) whilst multiplexes are becoming available for bacteraemia, pneumonia and gastrointestinal infection. These detect likely pathogens, but are not comprehensive, particularly for resistance genes; there is also the challenge of linking pathogens and resistance genes when multiple organisms are present in a sample. Next-generation sequencing offers more comprehensive profiling, but obstacles include sensitivity when the bacterial load is low, as in bacteraemia, and the imperfect correlation of genotype and phenotype. In short, rapid molecular bacteriology presents great potential to improve patient treatments and antibiotic stewardship but faces many technical challenges; moreover it runs counter to the current nostrum of defining resistance in pharmacodynamic terms, rather than by the presence of a mechanism, and the policy of centralising bacteriology services. | 2013 | 24265945 |
| 6691 | 4 | 0.9907 | The 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. | 2014 | 24795331 |
| 6664 | 5 | 0.9907 | Addressing 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. | 2025 | 40066274 |
| 9786 | 6 | 0.9907 | The CRISPR/Cas system as an antimicrobial resistance strategy in aquatic ecosystems. With the growing population, demand for food has dramatically increased, and fisheries, including aquaculture, are expected to play an essential role in sustaining demand with adequate quantities of protein and essential vitamin supplements, employment generation, and GDP growth. Unfortunately, the incidence of emerging/re-emerging AMR pathogens annually occurs because of anthropogenic activities and the frequent use of antibiotics in aquaculture. These AMR pathogens include the WHO's top 6 prioritized ESKAPE pathogens (nosocomial pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), extended-spectrum beta lactases (ESBLs) and carbapenemase-producing E. coli, which pose major challenges to the biomagnification of both nonnative and native antibiotic-resistant bacteria in capture and cultured fishes. Although implementing the rational use of antibiotics represents a promising mitigation measure, this approach is practically impossible due to the lack of awareness among farmers about the interplay between antimicrobial use and the emergence of antimicrobial resistance (AMR). Nevertheless, to eradicate these 'superbugs,' CRISPR/Cas (clustered regularly interspersed short palindromic repeats/CRISPR associate protein) has turned out to be a novel approach owing to its ability to perform precise site-directed targeting/knockdown/reversal of specific antimicrobial resistance genes in vitro and to distinguish AMR-resistant bacteria from a plethora of commensal aquatic bacteria. Along with highlighting the importance of virulent multidrug resistance genes in bacteria, this article aims to provide a holistic picture of CRISPR/Cas9-mediated genome editing for combating antimicrobial-resistant bacteria isolated from various aquaculture and marine systems, as well as insights into different types of CRISPR/Cas systems, delivery methods, and challenges associated with developing CRISPR/Cas9 antimicrobial agents. | 2024 | 38806846 |
| 2590 | 7 | 0.9907 | Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students. BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of 'stool and stories' that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR. METHODS: A longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel (T0, n = 45), in the first week in India (T1, n = 44), the second week in India (T2, n = 41); and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis. RESULTS: The incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling. CONCLUSION: The microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the 'stool and stories' approach is important for a transdisciplinary basis of AMR stewardship. | 2021 | 34579656 |
| 5826 | 8 | 0.9906 | Rapid and accurate sepsis diagnostics via a novel probe-based multiplex real-time PCR system. Sepsis is a critical clinical emergency that requires prompt diagnosis and intervention. Its prevalence has increased due to the aging population and increased antibiotic resistance. Early identification and the use of innovative technologies are crucial for improving patient outcomes. Modern methodologies are needed to minimize the turnaround time for diagnosis and improve outcomes. Rapid diagnostic tests and multiplex PCR are effective but have limitations in identifying a range of pathogens and target genes. Our study evaluated two novel probe-based multiplex real-time PCR systems: the SEPSI ID and SEPSI DR panels. These systems can quickly identify bacterial and fungal pathogens, alongside antibiotic resistance genes. The assays cover 29 microorganisms (gram-negative bacteria, gram-positive bacteria, yeast, and mold species), alongside 23 resistance genes and four virulence factors. A streamlined workflow uses 2 µL of broth from positive blood cultures (BCs) without nucleic acid extraction and provides results in approximately 1 h. We present the results from an evaluation of 228 BCs and 22 isolates previously characterized by whole-genome sequencing. In comparison to the reference methods, the SEPSI ID panel demonstrated a sensitivity of 96.88%, a specificity of 100%, and a PPV of 100%, whereas the SEPSI DR panel showed a sensitivity of 97.8%, a PPV of 89.7%, and a specificity of 96.7%. Both panels also identified additional pathogens and resistance-related targets not detected by conventional methods. This assay shows promise for rapidly and accurately diagnosing sepsis. Future studies should validate its performance in various clinical settings to enhance sepsis management and improve patient outcomes.IMPORTANCEWe present a new diagnostic method that enables the quick and precise identification of pathogens and resistance genes from positive blood cultures, eliminating the need for nucleic acid extraction. This technique can also be used on fresh pathogen cultures. It has the potential to greatly improve treatment protocols, leading to better patient outcomes, more responsible antibiotic use, and more efficient management of healthcare resources. | 2025 | 41025980 |
| 9076 | 9 | 0.9905 | ResiDB: An automated database manager for sequence data. The amount of publicly available DNA sequence data is drastically increasing, making it a tedious task to create sequence databases necessary for the design of diagnostic assays. The selection of appropriate sequences is especially challenging in genes affected by frequent point mutations such as antibiotic resistance genes. To overcome this issue, we have designed the webtool resiDB, a rapid and user-friendly sequence database manager for bacteria, fungi, viruses, protozoa, invertebrates, plants, archaea, environmental and whole genome shotgun sequence data. It automatically identifies and curates sequence clusters to create custom sequence databases based on user-defined input sequences. A collection of helpful visualization tools gives the user the opportunity to easily access, evaluate, edit, and download the newly created database. Consequently, researchers do no longer have to manually manage sequence data retrieval, deal with hardware limitations, and run multiple independent software tools, each having its own requirements, input and output formats. Our tool was developed within the H2020 project FAPIC aiming to develop a single diagnostic assay targeting all sepsis-relevant pathogens and antibiotic resistance mechanisms. ResiDB is freely accessible to all users through https://residb.ait.ac.at/. | 2021 | 33495705 |
| 5097 | 10 | 0.9904 | Comparing Graph Sample and Aggregation (SAGE) and Graph Attention Networks in the Prediction of Drug-Gene Associations of Extended-Spectrum Beta-Lactamases in Periodontal Infections and Resistance. INTRODUCTION: Gram-negative bacteria exhibit more antibiotic resistance than gram-positive bacteria due to their cell wall structure and composition differences. Porins, or protein channels in these bacteria, can allow small, hydrophilic antibiotics to diffuse, affecting their susceptibility. Mutations in porin protein genes can also impair antibiotic entry. Predicting drug-gene associations of extended-spectrum beta-lactamases (ESBLs) is crucial as they confer resistance to beta-lactam antibiotics, challenging the treatment of infections. This aids clinicians in selecting suitable treatments, optimizing drug usage, enhancing patient outcomes, and controlling antibiotic resistance in healthcare settings. Graph-based neural networks can predict drug-gene associations in periodontal infections and resistance. The aim of the study was to predict drug-gene associations of ESBLs in periodontal infections and resistance. METHODS: The study focuses on analyzing drug-gene associations using probes and drugs. The data was converted into graph language, assigning nodes and edges for drugs and genes. Graph neural networks (GNNs) and similar algorithms were implemented using Google Colab and Python. Cytoscape and CytoHubba are open-source software platforms used for network analysis and visualization. GNNs were used for tasks like node classification, link prediction, and graph-level prediction. Three graph-based models were used: graph convolutional network (GCN), Graph SAGE, and graph attention network (GAT). Each model was trained for 200 epochs using the Adam optimizer with a learning rate of 0.01 and a weight decay of 5e-4. RESULTS: The drug-gene association network has 57 nodes, 79 edges, and a 2.730 characteristic path length. Its structure, organization, and connectivity are analyzed using the GCN and Graph SAGE, which show high accuracy, precision, recall, and an F1-score of 0.94. GAT's performance metrics are lower, with an accuracy of 0.68, precision of 0.47, recall of 0.68, and F1-score of 0.56, suggesting that it may not be as effective in capturing drug-gene relationships. CONCLUSION: Compared to ESBLs, both GCN and Graph SAGE demonstrate excellent performance with accuracy, precision, recall, and an F1-score of 0.94. These results indicate that GCN and Graph SAGE are highly effective in predicting drug-gene associations related to ESBLs. GCN and Graph SAGE outperform GAT in predicting drug-gene associations for ESBLs. Improvements include data augmentation, regularization, and cross-validation. Ethical considerations, fairness, and open-source implementations are crucial for future research in precision periodontal treatment. | 2024 | 39347119 |
| 9808 | 11 | 0.9904 | Understanding Recent Developments in Colistin Resistance: Mechanisms, Clinical Implications, and Future Perspectives. Colistin resistance, driven by chromosomal mutations and the spread of plasmid-mediated MCR genes, has emerged as a critical challenge in combating multidrug-resistant Gram-negative bacteria. This resistance compromises the efficacy of colistin, leading to higher treatment failure rates, prolonged hospitalizations, and increased mortality. Recent studies have highlighted key mechanisms, including lipid A modifications, that enable bacteria to evade colistin's effects. The global spread of MCR genes exacerbates the issue, underlining the need for improved diagnostics and rapid detection of resistant strains to prevent adverse patient outcomes. To combat this growing threat, a multifaceted approach is essential, involving enhanced antimicrobial stewardship, stricter infection control measures, and continued research into alternative therapies and diagnostic methods. Collaborative efforts from researchers, healthcare providers, policymakers, and the pharmaceutical industry are crucial to preserving colistin's effectiveness and mitigating the broader impact on public health. | 2025 | 41148650 |
| 4886 | 12 | 0.9904 | Molecular 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. | 2023 | 36816746 |
| 8173 | 13 | 0.9904 | Advancing Antibacterial Strategies: CRISPR-Phage-Mediated Gene Therapy Targeting Bacterial Resistance Genes. One of the most significant issues facing the world today is antibiotic resistance, which makes it increasingly difficult to treat bacterial infections. Regular antibiotics no longer work against many bacteria, affecting millions of people. A novel approach known as CRISPR-phage therapy may be beneficial. This technique introduces a technology called CRISPR into resistant bacteria using bacteriophages. The genes that cause bacteria to become resistant to antibiotics can be identified and cut using CRISPR. This enables antibiotics to function by inhibiting the bacteria. This approach is highly precise, unlike conventional antibiotics, so it doesn't damage our bodies' beneficial bacteria. Preliminary studies and limited clinical trials suggest that this technique can effectively target drug-resistant bacteria such as Klebsiella pneumoniae and Methicillinresistant Staphylococcus aureus (MRSA). However, challenges in phage engineering, host delivery, and the growing threat of bacterial CRISPR resistance demand urgent and strategic innovation. Our perspective underscores that without proactive resolution of these hurdles, the current hopefulness could disappear. Looking ahead, integrating next-generation Cas effectors, non-DSB editors, and resistance monitoring frameworks could transform CRISPR-phage systems from an experimental novelty into a clinical mainstay. This shift will require not only scientific ingenuity but also coordinated advances in regulatory, translational, and manufacturing efforts. | 2025 | 40990280 |
| 5118 | 14 | 0.9903 | Automated extraction of genes associated with antibiotic resistance from the biomedical literature. The detection of bacterial antibiotic resistance phenotypes is important when carrying out clinical decisions for patient treatment. Conventional phenotypic testing involves culturing bacteria which requires a significant amount of time and work. Whole-genome sequencing is emerging as a fast alternative to resistance prediction, by considering the presence/absence of certain genes. A lot of research has focused on determining which bacterial genes cause antibiotic resistance and efforts are being made to consolidate these facts in knowledge bases (KBs). KBs are usually manually curated by domain experts to be of the highest quality. However, this limits the pace at which new facts are added. Automated relation extraction of gene-antibiotic resistance relations from the biomedical literature is one solution that can simplify the curation process. This paper reports on the development of a text mining pipeline that takes in English biomedical abstracts and outputs genes that are predicted to cause resistance to antibiotics. To test the generalisability of this pipeline it was then applied to predict genes associated with Helicobacter pylori antibiotic resistance, that are not present in common antibiotic resistance KBs or publications studying H. pylori. These genes would be candidates for further lab-based antibiotic research and inclusion in these KBs. For relation extraction, state-of-the-art deep learning models were used. These models were trained on a newly developed silver corpus which was generated by distant supervision of abstracts using the facts obtained from KBs. The top performing model was superior to a co-occurrence model, achieving a recall of 95%, a precision of 60% and F1-score of 74% on a manually annotated holdout dataset. To our knowledge, this project was the first attempt at developing a complete text mining pipeline that incorporates deep learning models to extract gene-antibiotic resistance relations from the literature. Additional related data can be found at https://github.com/AndreBrincat/Gene-Antibiotic-Resistance-Relation-Extraction. | 2022 | 35134132 |
| 2497 | 15 | 0.9903 | Rapid Simultaneous Detection of the Clinically Relevant Carbapenemase Resistance Genes blaKPC, blaOXA48, blaVIM and blaNDM with the Newly Developed Ready-to-Use qPCR CarbaScan LyoBead. Antibiotic resistance, in particular the dissemination of carbapenemase-producing organisms, poses a significant threat to global healthcare. This study introduces the qPCR CarbaScan LyoBead assay, a robust, accurate, and efficient tool for detecting key carbapenemase genes, including blaKPC, blaNDM, blaOXA-48, and blaVIM. The assay utilizes lyophilized beads, a technological advancement that enhances stability, simplifies handling, and eliminates the need for refrigeration. This feature renders it particularly well-suited for point-of-care diagnostics and resource-limited settings. The assay's capacity to detect carbapenemase genes directly from bacterial colonies without the need for extensive sample preparation has been demonstrated to streamline workflows and enable rapid diagnostic results. The assay demonstrated 100% specificity and sensitivity across a diverse range of bacterial strains, including multiple allelic variants of target genes, facilitating precise identification of resistance mechanisms. Bacterial strains of the species Acinetobacter baumannii, Citrobacter freundii, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa were utilized as reference material for assay development (n = 9) and validation (n = 28). It is notable that the assay's long shelf life and minimal operational complexity further enhance its utility for large-scale implementation in healthcare, food safety, and environmental monitoring. The findings emphasize the necessity of continuous surveillance and the implementation of rapid diagnostic methods for the effective detection of resistance genes. Furthermore, the assay's potential applications in other fields, such as toxin-antitoxin system research and monitoring of resistant bacteria in the community, highlight its versatility. In conclusion, the qPCR CarbaScan LyoBead assay is a valuable tool that can contribute to the urgent need to combat antibiotic resistance and improve global public health outcomes. | 2025 | 39940986 |
| 9810 | 16 | 0.9903 | Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies. Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathogens express different mechanisms of antimicrobial resistance. Clinicians face challenges in managing patients with multidrug-resistant bacteria in the form of a limited pool of available antibiotics, slow and potentially inaccurate conventional diagnostic microbial modalities, mimicry of non-infective conditions with infective syndromes, and the confounding of the clinical picture of organ dysfunction associated with sepsis with postoperative surgical complications such as hemorrhage and fluid shifts. Potential remedies for antimicrobial resistance include specific surveillance, adequate and systematic antibiotic stewardship, use of pharmacokinetic and pharmacodynamic techniques of therapy, and antimicrobial monitoring and adequate employment of infection control policies. Novel techniques of combating antimicrobial resistance include the use of aerosolized antibiotics for lung infections, the restoration of gut microflora using fecal transplantation, and orally administered probiotics. Newer antibiotics are urgently needed as part of the armamentarium against multidrug-resistant bacteria. In this review we discuss mechanisms and patterns of microbial resistance in a select group of drug-resistant bacteria, and preventive and remedial measures for combating antibiotic resistance in the critically ill. | 2023 | 39816646 |
| 9075 | 17 | 0.9903 | CamPype: 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 . | 2023 | 37474912 |
| 1539 | 18 | 0.9903 | WGS of a lytic phage targeting biofilm-forming carbapenem-resistant Klebsiella pneumoniae prevalent in a tertiary healthcare setup. Carbapenem-resistant Enterobacteriaceae (CRE) are listed as a priority-one critical pathogen category by the WHO because of their abysmal treatment outcomes owing to antibiotic inefficiency. Among CRE, Klebsiella pneumoniae is prevalent in acquiring resistance genes and withstanding the last-resort drugs. Additionally, its ability to form robust biofilms further exacerbates the treatment challenges. The escalating resistance and recalcitrance of biofilm-residing bacteria against standard antibiotic treatments demand an alternative to antibiotics. Phages, being nature-tailored, are a never-ending arsenal against the bacteria because of their capacity to lyse bacteria rapidly and co-evolve with bacteria. In our study, we isolated K. pneumoniae from patients at Madras Medical Mission Hospital (MMMH), India, and assessed their antibiogram profiles, presence of carbapenemase genes, and biofilm-forming abilities. 100 % of the strains were extended-spectrum beta-lactamase producing, multidrug-resistant (ESBL-MDR), with 95 % harbouring carbapenemase genes. Among the isolates, 65 % were strong biofilm formers, and the rest were moderate. Further, we isolated a bacteriophage, SAKp11, from the hospital sewage, which was able to lyse 62 out of 167 clinical isolates and successfully reduced 99.99 % viable bacterial cells of the 24-h-old biofilm of strong biofilm forming MDR K. pneumoniae strains. Whole genome analysis revealed that SAKp11, with a genome size of 59,338bp, belonged to the Casjensviridae family, one of the less explored bacteriophage families. Comprehensive characterization of SAKp11 indicated its suitability for therapeutic use. Our study highlights the severity of drug-resistant K. pneumoniae in Indian healthcare and the inadequacy of current antibiotics, underscoring the potential of phages as an alternative therapeutic option. | 2025 | 40348211 |
| 9760 | 19 | 0.9903 | Mutations leading to ceftolozane/tazobactam and imipenem/cilastatin/relebactam resistance during in vivo exposure to ceftazidime/avibactam in Pseudomonas aeruginosa. Identifying resistance mechanisms to novel antimicrobials informs treatment strategies during infection and antimicrobial development. Studying resistance that develops during the treatment of an infection can provide the most clinically relevant mutations conferring resistance, but cross-sectional studies frequently identify multiple candidate resistance mutations without resolving the driver mutation. We performed whole-genome sequencing of longitudinal Pseudomonas aeruginosa from a patient whose P. aeruginosa developed imipenem/cilastatin/relebactam and ceftolozane/tazobactam resistance during ceftazidime/avibactam treatment. This analysis determined new mutations that arose in isolates resistant to both imipenem/cilastatin/relebactam and ceftolozane/tazobactam. Mutations in penicillin-binding protein 3 ftsI, the MexAB-OprM repressor nalD, and a virulence regulator pvdS were found in resistant isolates. Importantly, drug efflux was not increased in the resistant isolate compared to the most closely related susceptible isolates. We conclude that mutations in peptidoglycan synthesis genes can alter the efficacy of multiple antimicrobials. IMPORTANCE: Antibiotic resistance is a significant challenge for physicians trying to treat infections. The development of novel antibiotics to treat resistant infections has not been prioritized for decades, limiting treatment options for infections caused by many high-priority pathogens. Cross-resistance, when one mutation provides resistance to multiple antibiotics, is most problematic. Mutations that cause cross-resistance need to be considered when developing new antibiotics to guide developers toward drugs with different targets, and thus a better likelihood of efficacy. This work was undertaken to determine the mutation that caused resistance to three antibiotics for highly resistant Pseudomonas aeruginosa infection treatment while the bacteria were exposed to only one of these agents. The findings provide evidence that drug developers should endeavor to find effective antibiotics with new targets and that medical providers should utilize medications with different mechanisms of action in bacteria that have become resistant to even one of these three agents. | 2025 | 39932323 |