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816100.9862Integrative 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.202540914328
922510.9858Antibiotic resistance modifying ability of phytoextracts in anthrax biological agent Bacillus anthracis and emerging superbugs: a review of synergistic mechanisms. BACKGROUND AND OBJECTIVES: The chemotherapeutic management of infections has become challenging due to the global emergence of antibiotic resistant pathogenic bacteria. The recent expansion of studies on plant-derived natural products has lead to the discovery of a plethora of phytochemicals with the potential to combat bacterial drug resistance via various mechanisms of action. This review paper summarizes the primary antibiotic resistance mechanisms of bacteria and also discusses the antibiotic-potentiating ability of phytoextracts and various classes of isolated phytochemicals in reversing antibiotic resistance in anthrax agent Bacillus anthracis and emerging superbug bacteria. METHODS: Growth inhibitory indices and fractional inhibitory concentration index were applied to evaluate the in vitro synergistic activity of phytoextract-antibiotic combinations in general. FINDINGS: A number of studies have indicated that plant-derived natural compounds are capable of significantly reducing the minimum inhibitory concentration of standard antibiotics by altering drug-resistance mechanisms of B. anthracis and other superbug infection causing bacteria. Phytochemical compounds allicin, oleanolic acid, epigallocatechin gallate and curcumin and Jatropha curcas extracts were exceptional synergistic potentiators of various standard antibiotics. CONCLUSION: Considering these facts, phytochemicals represents a valuable and novel source of bioactive compounds with potent antibiotic synergism to modulate bacterial drug-resistance.202134856999
981020.9856Drug-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.202339816646
818530.9855RNA-cleaving DNAzymes as a diagnostic and therapeutic agent against antimicrobial resistant bacteria. The development of nucleic-acid-based antimicrobials such as RNA-cleaving DNAzyme (RCD), a short catalytically active nucleic acid, is a promising alternative to the current antibiotics. The current rapid spread of antimicrobial resistance (AMR) in bacteria renders some antibiotics useless against bacterial infection, thus creating the need for alternative antimicrobials such as DNAzymes. This review summarizes recent advances in the use of RCD as a diagnostic and therapeutic agent against AMR. Firstly, the recent diagnostic application of RCD for the detection of bacterial cells and the associated resistant gene(s) is discussed. The next section summarises the therapeutic application of RCD in AMR bacterial infections which includes direct targeting of the resistant genes and indirect targeting of AMR-associated genes. Finally, this review extends the discussion to challenges of utilizing RCD in real-life applications, and the potential of combining both diagnostic and therapeutic applications of RCD into a single agent as a theranostic agent.202234505182
818040.9854Harnessing Nanoparticles to Overcome Antimicrobial Resistance: Promises and Challenges. The rise of antimicrobial resistance (AMR) has become a serious global health issue that kills millions of people each year globally. AMR developed in bacteria is difficult to treat and poses a challenge to clinicians. Bacteria develop resistance through a variety of processes, including biofilm growth, targeted area alterations, and therapeutic drug alteration, prolonging the period they remain within cells, where antibiotics are useless at therapeutic levels. This rise in resistance is linked to increased illness and death, highlighting the urgent need for effective solutions to combat this growing challenge. Nanoparticles (NPs) offer unique solutions for fighting AMR bacteria. Being smaller in size with a high surface area, enhancing interaction with bacteria makes the NPs strong antibacterial agents against various infections. In this review, we have discussed the epidemiology and mechanism of AMR development. Furthermore, the role of nanoparticles as antibacterial agents, and their role in drug delivery has been addressed. Additionally, the potential, challenges, toxicity, and future prospects of nanoparticles as antibacterial agents against AMR pathogens have been discussed. The research work discussed in this review links with Sustainable Development Goal 3 (SDG-3), which aims to ensure disease-free lives and promote well-being for all ages.202539219123
815850.9854Nanobioconjugates: Weapons against Antibacterial Resistance. The increase in drug resistance in pathogenic bacteria is emerging as a global threat as we swiftly edge toward the postantibiotic era. Nanobioconjugates have gained tremendous attention to treat multidrug-resistant (MDR) bacteria and biofilms due to their tunable physicochemical properties, drug targeting ability, enhanced uptake, and alternate mechanisms of drug action. In this review, we highlight the recent advances made in the use of nanobioconjugates to combat antibacterial resistance and provide crucial insights for designing nanomaterials that can serve as antibacterial agents for nanotherapeutics, nanocargos for targeted antibiotic delivery, or both. Also discussed are different strategies for treating robust biofilms formed by bacteria.202035019602
980860.9854Understanding 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.202541148650
817670.9853Overcoming Multidrug Resistance in Bacteria Through Antibiotics Delivery in Surface-Engineered Nano-Cargos: Recent Developments for Future Nano-Antibiotics. In the recent few decades, the increase in multidrug-resistant (MDR) bacteria has reached an alarming rate and caused serious health problems. The incidence of infections due to MDR bacteria has been accompanied by morbidity and mortality; therefore, tackling bacterial resistance has become an urgent and unmet challenge to be properly addressed. The field of nanomedicine has the potential to design and develop efficient antimicrobials for MDR bacteria using its innovative and alternative approaches. The uniquely constructed nano-sized antimicrobials have a predominance over traditional antibiotics because their small size helps them in better interaction with bacterial cells. Moreover, surface engineering of nanocarriers offers significant advantages of targeting and modulating various resistance mechanisms, thus owe superior qualities for overcoming bacterial resistance. This review covers different mechanisms of antibiotic resistance, application of nanocarrier systems in drug delivery, functionalization of nanocarriers, application of functionalized nanocarriers for overcoming bacterial resistance, possible limitations of nanocarrier-based approach for antibacterial delivery, and future of surface-functionalized antimicrobial delivery systems.202134307323
665380.9852Making 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
818290.9852Antibiotics in Food Chain: The Consequences for Antibiotic Resistance. Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.202033066005
8175100.9852Role of Nanocarrier Systems in Drug Delivery for Overcoming Multi-Drug Resistance in Bacteria. Multidrug-resistant (MDR) bacteria have risen alarmingly in the last few decades, posing a serious threat to human health. The need for effective bacterial resistance treatment is urgent and unmet due to the rise in morbidity and mortality that has coincided with the prevalence of infections caused by MDR bacteria. Using its creative and unconventional methods, effective antibiotics for MDR bacteria could be developed using nanomedicine techniques. To combat microbial resistance, a number of strategies have been developed, including the use of natural bactericides, the introduction of fresh antibiotics, the application of combination therapy and the creation of NP-based antibiotic nanocarriers. The absence of novel antibacterial agents has worsened the situation for MDR bacteria. Ineffective antibiotics used to treat MDR bacteria also contribute to the bacteria's tolerance growing. Nanoparticles (NPs) are the most efficient method for eliminating MDR bacteria because they serve as both carriers of natural antibiotics and antimicrobials and active agents against bacteria. Additionally, surface engineering of nanocarriers has important benefits for focusing on and modifying a variety of resistance mechanisms. The use of nanocarrier systems in drug delivery for overcoming bacterial resistance is covered in this review along with various mechanisms of antibiotic resistance.202337480270
8134110.9852Sweet scents from good bacteria: Case studies on bacterial volatile compounds for plant growth and immunity. Beneficial bacteria produce diverse chemical compounds that affect the behavior of other organisms including plants. Bacterial volatile compounds (BVCs) contribute to triggering plant immunity and promoting plant growth. Previous studies investigated changes in plant physiology caused by in vitro application of the identified volatile compounds or the BVC-emitting bacteria. This review collates new information on BVC-mediated plant-bacteria airborne interactions, addresses unresolved questions about the biological relevance of BVCs, and summarizes data on recently identified BVCs that improve plant growth or protection. Recent explorations of bacterial metabolic engineering to alter BVC production using heterologous or endogenous genes are introduced. Molecular genetic approaches can expand the BVC repertoire of beneficial bacteria to target additional beneficial effects, or simply boost the production level of naturally occurring BVCs. The effects of direct BVC application in soil are reviewed and evaluated for potential large-scale field and agricultural applications. Our review of recent BVC data indicates that BVCs have great potential to serve as effective biostimulants and bioprotectants even under open-field conditions.201626177913
9447120.9852Modern vaccine development via reverse vaccinology to combat antimicrobial resistance. With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review.202235642852
6664130.9851Addressing 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
9441140.9850Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace. BACKGROUND: Antibiotic resistance is currently the most serious global threat to the effective treatment of bacterial infections. Antibiotic resistance has been established to adversely affect both clinical and therapeutic outcomes, with consequences ranging from treatment failures and the need for expensive and safer alternative drugs to the cost of higher rates of morbidity and mortality, longer hospitalization, and high-healthcare costs. The search for new antibiotics and other antimicrobials continues to be a pressing need in humanity's battle against bacterial infections. Antibiotic resistance appears inevitable, and there is a continuous lack of interest in investing in new antibiotic research by pharmaceutical industries. This review summarized some new strategies for tackling antibiotic resistance in bacteria. METHODS: To provide an overview of the recent research, we look at some new strategies for preventing resistance and/or reviving bacteria's susceptibility to already existing antibiotics. RESULTS: Substantial pieces of evidence suggest that antimicrobials interact with host immunity, leading to potent indirect effects that improve antibacterial activities and may result in more swift and complete bactericidal effects. A new class of antibiotics referred to as immuno-antibiotics and the targeting of some biochemical resistance pathway components including inhibition of SOS response and hydrogen sulfide as biochemical underlying networks of bacteria can be considered as new emerging strategies to combat antibiotic resistance in bacteria. CONCLUSION: This review highlighted and discussed immuno-antibiotics and inhibition of SOS response and hydrogen sulfide as biochemical underlying networks of bacteria as new weapons against antibiotic resistance in bacteria.202235949048
6608150.9850Trends in antimicrobial resistance in Malaysia. INTRODUCTION: Antibiotic resistance is a burgeoning problem worldwide. The trend of bacterial resistance has increased over the past decade in which more common bacteria are becoming resistant to almost all the antibiotics currently in use, posing a threat to humans and even livestock. METHODS: The databases used to search for the relevant articles for this review include PubMed, Science Direct, and Scopus. The following keywords were used in the search: Antimicrobial resistance, Malaysian action plan, antibioticresistant bacteria, and Malaysian National Surveillance on Antimicrobial Resistance (NSAR). The relevant articles published in English were considered. RESULTS: The antibiotic-resistant bacteria highlighted in this review showed an increase in resistance patterns to the majority of the antibiotics tested. The Malaysian government has come up with an action plan to create public awareness and to educate them regarding the health implications of antibiotic resistance. CONCLUSION: Antimicrobial resistance in Malaysia continues to escalate and is attributed to the overuse and misuse of antibiotics in various fields. As this crisis impacts the health of both humans and animals, therefore a joined continuous effort from all sectors is warranted to reduce the spread and minimize its development.202134508377
8179160.9850Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives. The wide spread of antibiotic resistance has been alarming in recent years and poses a serious global hazard to public health as it leads to millions of deaths all over the world. The wide spread of resistance and sharing resistance genes between different types of bacteria led to emergence of multidrug resistant (MDR) microorganisms. This problem is exacerbated when microorganisms create biofilms, which can boost bacterial resistance by up to 1000-fold and increase the emergence of MDR infections. The absence of novel and potent antimicrobial compounds is linked to the rise of multidrug resistance. This has sparked international efforts to develop new and improved antimicrobial agents as well as innovative and efficient techniques for antibiotic administration and targeting. There is an evolution in nanotechnology in recent years in treatment and prevention of the biofilm formation and MDR infection. The development of nanomaterial-based therapeutics, which could overcome current pathways linked to acquired drug resistance, is a hopeful strategy for treating difficult-to-treat bacterial infections. Additionally, nanoparticles' distinct size and physical characteristics enable them to target biofilms and treat resistant pathogens. This review highlights the current advances in nanotechnology to combat MDR and biofilm infection. In addition, it provides insight on development and mechanisms of antibiotic resistance, spread of MDR and XDR infection, and development of nanoparticles and mechanisms of their antibacterial activity. Moreover, this review considers the difference between free antibiotics and nanoantibiotics, and the synergistic effect of nanoantibiotics to combat planktonic bacteria, intracellular bacteria and biofilm. Finally, we will discuss the strength and limitations of the application of nanotechnology against bacterial infection and future perspectives.202336830949
6672170.9850Antibiotic resistance in bacteria - an emerging public health problem. The discovery and eventual introduction of anti-microbial agents to clinical medicine was one of the greatest medical triumphs of the twentieth century that revolutionized the treatment of bacterial diseases. However, the gradual emergence of populations of antibiotic-resistant bacteria resulting from use, misuse and outright abuse of antibiotics has today become a major public health problem of global proportions. This review paper examines the origins and molecular epidemiology of resistance genes, global picture of antibacterial resistance, factors that favour its spread, strategies for its control, problems of control and the consequences of failure to contain antibiotic resistance in bacteria.200327528961
8178180.9850Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions. Antimicrobial resistance is a global health threat. Misuse and overuse of antimicrobials are the main drivers in developing drug-resistant bacteria. The emergence of the rapid global spread of multi-resistant bacteria requires urgent multisectoral action to generate novel treatment alternatives. Combination therapy offers the potential to exploit synergistic effects for enhanced antibacterial efficacy of drugs. Understanding the complex dynamics and kinetics of drug interactions in combination therapy is crucial. Therefore, this review outlines the current advances in antibiotic resistance's evolutionary and genetic dynamics in combination therapies-exposed bacteria. Moreover, we also discussed four pivotal future research areas to comprehend better the development of antibiotic resistance in bacteria treated with combination strategies.202438510041
6657190.9850From 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