# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8161 | 0 | 0.9879 | 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 |
| 8160 | 1 | 0.9862 | Quorum Sensing in Gram-Negative Bacteria: Strategies to Overcome Antibiotic Resistance in Ocular Infections. Truly miraculous medications and antibiotics have helped save untold millions of lives. Antibiotic resistance, however, is a significant issue related to health that jeopardizes the effectiveness of antibiotics and could harm everyone's health. Bacteria, not humans or animals, become antibiotic-resistant. Bacteria use quorum-sensing communication routes to manage an assortment of physiological exercises. Quorum sensing is significant for appropriate biofilm development. Antibiotic resistance occurs when bacteria establish a biofilm on a surface, shielding them from the effects of infection-fighting drugs. Acylated homoserine lactones are used as autoinducers by gram-negative microscopic organisms to impart. However, antibiotic resistance among ocular pathogens is increasing worldwide. Bacteria are a significant contributor to ocular infections around the world. Gram-negative microscopic organisms are dangerous to ophthalmic tissues. This review highlights the use of elective drug targets and treatments, for example, combinational treatment, to vanquish antibiotic-resistant bacteria. Also, it briefly portrays anti-biotic resistance brought about by gram-negative bacteria and approaches to overcome resistance with the help of quorum sensing inhibitors and nanotechnology as a promising medication conveyance approach to give insurance of anti-microbials and improve pathways for the administration of inhibitors of quorum sensing with a blend of anti-microbials to explicit target destinations and penetration through biofilms for treatment of ocular infections. It centres on the methodologies to sidestep the confinements of ocular anti-biotic delivery with new visual innovation. | 2024 | 37497706 |
| 9808 | 2 | 0.9858 | 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 |
| 8173 | 3 | 0.9857 | 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 |
| 223 | 4 | 0.9856 | Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria. Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy. | 2023 | 37760679 |
| 9446 | 5 | 0.9856 | Newer antibiotics for the treatment of respiratory tract infections. PURPOSE OF REVIEW: In this review, we highlight some of the developments achieved over the past 2 years in the field of novel antimicrobial compounds. RECENT FINDINGS: Modification of existing compound classes to create more powerful compounds capable of overcoming pathogen resistance and the introduction of completely new classes of antibiotics and inhibitors of new bacterial targets or inhibitors of genes relating to virulence or pathogenesis are the strategies more commonly employed in pharmacologic research. Ketolides, oxazolidinones, streptogramins, glycylcyclines, and peptide deformylase inhibitors are among the most promising classes of antibiotics. Recently, several lines of research have documented that it is effective to target the infection process rather than killing bacteria. This is important because it is likely that such a therapeutic strategy could ablate infection without inducing resistance. SUMMARY: Emergence of resistance to the antibiotics currently employed in clinical practice is a continual stimulus for further research aimed at identifying novel antimicrobial compounds. These drugs will perhaps effectively fight against bacteria that now are scarcely controlled by the traditional antimicrobial agents. Health care personnel must appreciate that only judicious use of antimicrobial drugs will prevent the further uncontrolled spread of bacterial resistance. Implementation of reference guidelines would probably be an effective way to limit antibiotic misuse. | 2004 | 15071370 |
| 9445 | 6 | 0.9855 | Bacteriophages of Mycobacterium tuberculosis, their diversity, and potential therapeutic uses: a review. Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a highly infectious disease and worldwide health problem. Based on the WHO TB report, 9 million active TB cases are emerging, leading to 2 million deaths each year. The recent emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains emphasizes the necessity to improve novel therapeutic plans. Among the various developing antibacterial approaches, phage therapy is thought to be a precise hopeful resolution. Mycobacteriophages are viruses that infect bacteria such as Mycobacterium spp., containing the M. tuberculosis complex. Phages and phage-derived proteins can act as promising antimicrobial agents. Also, phage cocktails can broaden the spectrum of lysis activity against bacteria. Recent researches have also shown the effective combination of antibiotics and phages to defeat the infective bacteria. There are limitations and concerns about phage therapy. For example, human immune response to phage therapy, transferring antibiotic resistance genes, emerging resistance to phages, and safety issues. So, in the present study, we introduced mycobacteriophages, their use as therapeutic agents, and their advantages and limitations as therapeutic applications. | 2022 | 36550444 |
| 9099 | 7 | 0.9855 | Small molecule downregulation of PmrAB reverses lipid A modification and breaks colistin resistance. Infections caused by multi-drug resistant bacteria, particularly Gram-negative bacteria, are an ever-increasing problem. While the development of new antibiotics remains one option in the fight against bacteria that have become resistant to currently available antibiotics, an attractive alternative is the development of adjuvant therapeutics that restore the efficacy of existing antibiotics. We report a small molecule adjuvant that suppresses colistin resistance in multidrug resistant Acinetobacter baumannii and Klebsiella pneumoniae by interfering with the expression of a two-component system. The compound downregulates the pmrCAB operon and reverses phosphoethanolamine modification of lipid A responsible for colistin resistance. Furthermore, colistin-susceptible and colistin-resistant bacteria do not evolve resistance to combination treatment. This represents the first definitive example of a compound that breaks antibiotic resistance by directly modulating two-component system activity. | 2014 | 24131198 |
| 9734 | 8 | 0.9854 | Combination of genetically diverse Pseudomonas phages enhances the cocktail efficiency against bacteria. Phage treatment has been used as an alternative to antibiotics since the early 1900s. However, bacteria may acquire phage resistance quickly, limiting the use of phage treatment. The combination of genetically diverse phages displaying distinct replication machinery in phage cocktails has therefore become a novel strategy to improve therapeutic outcomes. Here, we isolated and studied lytic phages (SPA01 and SPA05) that infect a wide range of clinical Pseudomonas aeruginosa isolates. These relatively small myophages have around 93 kbp genomes with no undesirable genes, have a 30-min latent period, and reproduce a relatively high number of progenies, ranging from 218 to 240 PFU per infected cell. Even though both phages lyse their hosts within 4 h, phage-resistant bacteria emerge during the treatment. Considering SPA01-resistant bacteria cross-resist phage SPA05 and vice versa, combining SPA01 and SPA05 for a cocktail would be ineffective. According to the decreased adsorption rate of the phages in the resistant isolates, one of the anti-phage mechanisms may occur through modification of phage receptors on the target cells. All resistant isolates, however, are susceptible to nucleus-forming jumbophages (PhiKZ and PhiPA3), which are genetically distinct from phages SPA01 and SPA05, suggesting that the jumbophages recognize a different receptor during phage entry. The combination of these phages with the jumbophage PhiKZ outperforms other tested combinations in terms of bactericidal activity and effectively suppresses the emergence of phage resistance. This finding reveals the effectiveness of the diverse phage-composed cocktail for reducing bacterial growth and prolonging the evolution of phage resistance. | 2023 | 37264114 |
| 9505 | 9 | 0.9854 | Heritable nanosilver resistance in priority pathogen: a unique genetic adaptation and comparison with ionic silver and antibiotics. The past decade has seen the incorporation of antimicrobial nanosilver (NAg) into medical devices, and, increasingly, in everyday 'antibacterial' products. With the continued rise of antibiotic resistant bacteria, there are concerns that these priority pathogens will also develop resistance to the extensively commercialized nanoparticle antimicrobials. Herein, this work reports the emergence of stable resistance traits to NAg in the WHO-listed priority pathogen Staphylococcus aureus, which has previously been suggested to have no, or very low, capacity for silver resistance. With no native presence of genetically encoded silver defence mechanisms, the work showed that the bacterium is dependent on mutation of physiologically essential genes, including those involved in nucleotide synthesis and oxidative stress defence. While some mutations were uniquely associated with resistance to NAg, the study also found common mutations that could be protective against both NAg and ionic silver. This is consistent with the observation of NAg/ionic silver cross-resistance. These mutations were detected following withdrawal of the silver exposure, denoting heritable characteristics that allow for spread of the resistance traits even with discontinued silver use. Heritable silver resistance in priority pathogen cautions that these nanoparticle antimicrobials should only be used as needed, to preserve their efficacy for treating infections. | 2020 | 31930233 |
| 8158 | 10 | 0.9854 | Nanobioconjugates: 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. | 2020 | 35019602 |
| 9752 | 11 | 0.9854 | Engineered Phages and Engineered and Recombinant Endolysins Against Carbapenem-Resistant Gram-Negative Bacteria: A Focused Review on Novel Antibacterial Strategies. Antibiotic resistance has escalated globally, affecting not only commonly used antibiotics but also last-resort agents such as carbapenems and colistin. The rise of antibiotic-resistant bacteria has prompted microbiologists to devise new strategies, with bacteriophages emerging as one of the most promising options. Nevertheless, certain mechanisms have been identified in bacteria that confer resistance to phages. While phage resistance is currently less widespread than antibiotic resistance, challenges such as biofilm formation, newly emerging resistance mechanisms against phages, and the natural limitations of unmodified phages have driven the advancement of engineered phages. This study aims to examine the efficacy of engineered phages and both engineered and recombinant endolysins against carbapenem-resistant Gram-negative bacteria (CR-GNB). We performed a literature review through PubMed, Scopus, Web of Science, and Google Scholar, concentrating on studies that utilized these agents against carbapenem-resistant Gram-negative bacteria (CR-GNB). Reviewed studies indicate potential antibacterial activity of these agents against CR-GNB. By engineering and modifying phages, these agents exhibit improved antimicrobial efficacy, temperature stability, and membrane permeability. Furthermore, they demonstrate the ability to eliminate bacteria with multidrug-resistant (MDR) and extensively drug-resistant (XDR) profiles. These findings suggest the promising potential of engineered phages and endolysins for future clinical applications against CR-GNB. | 2025 | 40696543 |
| 8176 | 12 | 0.9854 | Overcoming 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. | 2021 | 34307323 |
| 6649 | 13 | 0.9853 | 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 |
| 9796 | 14 | 0.9853 | Bacteriophage therapy to combat MDR non-fermenting Gram-negative bacteria causing nosocomial infections: recent progress and challenges. Clinicians face significant challenges in managing nosocomial infections, primarily due to antimicrobial resistance in multidrug-resistant bacteria. Regardless of the availability of a wide range of antimicrobials in the market, resistance is escalating rampantly with every passing day, which has become a global concern. Hence, it is essential to discover new and more efficient techniques to eliminate pathogens from healthcare settings. Along with eliminating pathogenic bacteria, mitigating their antimicrobial resistance with novel methods is very essential. Recently, bacteriophages have re-emerged as a promising therapeutic alternative to treat serious infections caused by bacterial pathogens. Bacteriophages were discovered for the first time a century ago, but their usage has recently regained more attention in treating bacterial pathogens. Bacteriophages also help in mitigating the worldwide problem of antibiotic resistance, particularly augmented by Gram-negative bacteria. This review discussed the advancements in the usage of bacteriophages in combating the antimicrobial resistance of multidrug-resistant Gram-negative bacteria, with a prime focus on Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cepacia complex (Bcc), which are renowned non-fermenting Gram-negative bacteria (NFGNB) pathogens. Additionally, the effects of single phage, phage cocktails, and combination therapy with antibiotics on bacterial biofilms and polymicrobial biofilms are also discussed. | 2025 | 40478338 |
| 9810 | 15 | 0.9853 | 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 |
| 9192 | 16 | 0.9852 | Antimicrobial peptides: Sustainable application informed by evolutionary constraints. The proliferation and global expansion of multidrug-resistant (MDR) bacteria have deepened the need to develop novel antimicrobials. Antimicrobial peptides (AMPs) are regarded as promising antibacterial agents because of their broad-spectrum antibacterial activity and multifaceted mechanisms of action with non-specific targets. However, if AMPs are to be applied sustainably, knowledge of how they induce resistance in pathogenic bacteria must be mastered to avoid repeating the traditional antibiotic resistance mistakes currently faced. Furthermore, the evolutionary constraints on the acquisition of AMP resistance by microorganisms in the natural environment, such as functional compatibility and fitness trade-offs, inform the translational application of AMPs. Consequently, the shortcut to achieve sustainable utilization of AMPs is to uncover the evolutionary constraints of bacteria on AMP resistance in nature and find the tricks to exploit these constraints, such as applying AMP cocktails to minimize the efficacy of selection for resistance or combining nanomaterials to maximize the costs of AMP resistance. Altogether, this review dissects the benefits, challenges, and opportunities of utilizing AMPs against disease-causing bacteria, and highlights the use of AMP cocktails or nanomaterials to proactively address potential AMP resistance crises in the future. | 2022 | 35752270 |
| 8167 | 17 | 0.9852 | Metal complexes against multidrug-resistant bacteria: recent advances (2020-present). The increasing prevalence of multidrug-resistant (MDR) bacterial infections worldwide represents a critical challenge to contemporary healthcare, with high mortality rates attributed primarily to biofilm formation and the widespread dissemination of antibiotic resistance genes. Metal complexes have emerged as promising candidates for combating resistant pathogens owing to their distinctive multi-target mechanisms. These compounds demonstrate dual functionality by effectively penetrating bacterial biofilms while simultaneously exerting antimicrobial effects through multiple pathways, including the production of reactive oxygen species (ROS) and interference with essential metal homeostasis. The growing inadequacy of conventional antibiotics against resistant infections necessitates the development of novel metal-based antimicrobial agents with low resistance propensity, high efficacy, and minimal toxicity profiles. The clinical validation of metallodrugs like auranofin provides a crucial foundation for designing next-generation anti-MDR therapeutics. Notably, complexes of gold (Au), silver (Ag), copper (Cu), gallium (Ga), iridium (Ir), and ruthenium (Ru) demonstrate multifaceted mechanisms of action through selective targeting of bacterial resistance mechanisms. These attributes enable them to provide a strategic framework for developing next-generation metal-based antibacterials. This review systematically summarizes the recent advances (2020-present) in the design and application of the complexes of these six metals against MDR bacteria, emphasizing their structural motifs, antimicrobial potency, and mechanistic insights. The presented insights provide novel approaches to combat the intensifying global challenge of antibiotic resistance. | 2025 | 41091096 |
| 9539 | 18 | 0.9852 | Materials for restoring lost Activity: Old drugs for new bugs. The escalation of bacterial resistance to conventional medical antibiotics is a serious concern worldwide. Improvements to current therapies are urgently needed to address this problem. The synergistic combination of antibiotics with other agents is a strategic solution to combat multi-drug-resistant bacteria. Although these combinations decrease the required high dosages and therefore, reduce the toxicity of both agents without compromising the bactericidal effect, they cannot stop the development of further resistance. Recent studies have shown certain elements restore the ability of antibiotics to destroy bacteria that have acquired resistance to them. Due to these synergistic activities, organic and inorganic molecules have been investigated with the goal of restoring antibiotics in new approaches that mitigate the risk of expanding resistance. Herein, we summarize recent studies that restore antibiotics once thought to be ineffective, but have returned to our armamentarium through innovative, combinatorial efforts. A special focus is placed on the mechanisms that allow the synergistic combinations to combat bacteria. The promising data that demonstrated restoration of antimicrobials, supports the notion to find more combinations that can combat antibiotic-resistant bacteria. | 2022 | 35461913 |
| 6650 | 19 | 0.9852 | 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 |