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980800.9979Understanding 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
660810.9978Trends 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
661620.9978The menace of colistin resistance across globe: Obstacles and opportunities in curbing its spread. Colistin-resistance in bacteria is a big concern for public health, since it is a last resort antibiotic to treat infectious diseases of multidrug resistant and carbapenem resistant Gram-negative pathogens in clinical settings. The emergence of colistin resistance in aquaculture and poultry settings has escalated the risks associated with colistin resistance in environment as well. The staggering number of reports pertaining to the rise of colistin resistance in bacteria from clinical and non-clinical settings is disconcerting. The co-existence of colistin resistant genes with other antibiotic resistant genes introduces new challenges in combatting antimicrobial resistance. Some countries have banned the manufacture, sale and distribution of colistin and its formulations for food producing animals. However, to tackle the issue of antimicrobial resistance, a one health approach initiative, inclusive of human, animal, and environmental health needs to be developed. Herein, we review the recent reports in colistin resistance in bacteria of clinical and non-clinical settings, deliberating on the new findings obtained regarding the development of colistin resistance. This review also discusses the initiatives implemented globally in mitigating colistin resistance, their strength and weakness.202336812837
817530.9978Role 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
488840.9978A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques. Infectious disease outbreaks have caused thousands of deaths and hospitalizations, along with severe negative global economic impacts. Among these, infections caused by antimicrobial-resistant microorganisms are a major growing concern. The misuse and overuse of antimicrobials have resulted in the emergence of antimicrobial resistance (AMR) worldwide. Carbapenem-resistant Enterobacterales (CRE) are among the bacteria that need urgent attention globally. The emergence and spread of carbapenem-resistant bacteria are mainly due to the rapid dissemination of genes that encode carbapenemases through horizontal gene transfer (HGT). The rapid dissemination enables the development of host colonization and infection cases in humans who do not use the antibiotic (carbapenem) or those who are hospitalized but interacting with environments and hosts colonized with carbapenemase-producing (CP) bacteria. There are continuing efforts to characterize and differentiate carbapenem-resistant bacteria from susceptible bacteria to allow for the appropriate diagnosis, treatment, prevention, and control of infections. This review presents an overview of the factors that cause the emergence of AMR, particularly CRE, where they have been reported, and then, it outlines carbapenemases and how they are disseminated through humans, the environment, and food systems. Then, current and emerging techniques for the detection and surveillance of AMR, primarily CRE, and gaps in detection technologies are presented. This review can assist in developing prevention and control measures to minimize the spread of carbapenem resistance in the human ecosystem, including hospitals, food supply chains, and water treatment facilities. Furthermore, the development of rapid and affordable detection techniques is helpful in controlling the negative impact of infections caused by AMR/CRE. Since delays in diagnostics and appropriate antibiotic treatment for such infections lead to increased mortality rates and hospital costs, it is, therefore, imperative that rapid tests be a priority.202337374993
979650.9978Bacteriophage 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.202540478338
665760.9978From 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
818170.9977Bacterial resistance to antibacterial agents: Mechanisms, control strategies, and implications for global health. The spread of bacterial drug resistance has posed a severe threat to public health globally. Here, we cover bacterial resistance to current antibacterial drugs, including traditional herbal medicines, conventional antibiotics, and antimicrobial peptides. We summarize the influence of bacterial drug resistance on global health and its economic burden while highlighting the resistance mechanisms developed by bacteria. Based on the One Health concept, we propose 4A strategies to combat bacterial resistance, including prudent Application of antibacterial agents, Administration, Assays, and Alternatives to antibiotics. Finally, we identify several opportunities and unsolved questions warranting future exploration for combating bacterial resistance, such as predicting genetic bacterial resistance through the use of more effective techniques, surveying both genetic determinants of bacterial resistance and the transmission dynamics of antibiotic resistance genes (ARGs).202336435256
249280.9977Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention. Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.202235979498
665890.9977Antibiotic Resistant Superbugs: Assessment of the Interrelationship of Occurrence in Clinical Settings and Environmental Niches. The increasing threat to global health posed by antibiotic resistance remains of serious concern. Human health remains at higher risk due to several reported therapeutic failures to many life threatening drug resistant microbial infections. The resultant effects have been prolonged hospital stay, higher cost of alternative therapy, increased mortality, etc. This opinionated review considers the two main concerns in integrated human health risk assessment (i.e., residual antibiotics and antibiotic resistant genes) in various compartments of human environment, as well as clinical dynamics associated with the development and transfer of antibiotic resistance (AR). Contributions of quorum sensing, biofilms, enzyme production, and small colony variants in bacteria, among other factors in soil, water, animal farm and clinical settings were also considered. Every potential factor in environmental and clinical settings that brings about AR needs to be identified for the summative effects in overall resistance. There is a need to embrace coordinated multi-locational approaches and interrelationships to track the emergence of resistance in different niches in soil and water versus the hospital environment. The further integration with advocacy, legislation, enforcement, technological innovations and further research input and recourse to WHO guidelines on antibiotic policy would be advantageous towards addressing the emergence of antibiotic resistant superbugs.201628035988
9795100.9977Antibiotic resistance: how it arises, the current position and strategies for the future. After 70 years of antibiotic therapy, the threat of untreatable infections is again a reality with resistance to antibiotics increasing in both Gram positive and Gram negative bacteria. Antibiotic-resistant bacteria cause both community and healthcare associated infections, presenting challenges in treatment and management. The development of new and novel antibiotics, particularly for Gram negative bacteria, is worryingly lacking. This article reviews the current situation and examines future strategies to tackle the continued threat of bacterial resistance.200919835196
4889110.9977The Challenge of Overcoming Antibiotic Resistance in Carbapenem-Resistant Gram-Negative Bacteria: "Attack on Titan". The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multidrug-resistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance genes, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.202337630472
4332120.9977Development and transmission of antimicrobial resistance among Gram-negative bacteria in animals and their public health impact. Gram-negative bacteria are known to cause severe infections in both humans and animals. Antimicrobial resistance (AMR) in Gram-negative bacteria is a major challenge in the treatment of clinical infections globally due to the propensity of these organisms to rapidly develop resistance against antimicrobials in use. In addition, Gram-negative bacteria possess highly efficient mechanisms through which the AMR can be disseminated between pathogenic and commensal bacteria of the same or different species. These unique traits of Gram-negative bacteria have resulted in evolution of Gram-negative bacterial strains demonstrating resistance to multiple classes of antimicrobials. The evergrowing resistance issue has not only resulted in limitation of treatment options but also led to increased treatment costs and mortality rates in humans and animals. With few or no new antimicrobials in production to combat severe life-threatening infections, AMR has been described as the one of the most severe, long-term threats to human health. Aside from overuse and misuse of antimicrobials in humans, another factor that has exacerbated the emergence of AMR in Gram-negative bacteria is the veterinary use of antimicrobials that belong to the same classes considered to be critically important for treating serious life-threatening infections in humans. Despite the fact that development of AMR dates back to before the introduction of antimicrobials, the recent surge in the resistance towards all available critically important antimicrobials has emerged as a major public health issue. This review thus focuses on discussing the development, transmission and public health impact of AMR in Gram-negative bacteria in animals.201728258227
9752130.9977Engineered 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.202540696543
4887140.9977Mechanisms of Bacterial Drug Resistance with Special Emphasis on Phenotypic and Molecular Characterization of Extended Spectrum Beta-lactamase. Antibiotics are designed to effectively treat bacterial infections while minimizing harm to the human body. They work by targeting specific components of bacteria or by disrupting essential processes such as cell wall synthesis, membrane function, protein production, and metabolic pathways. However, the misuse and overuse of antibiotics have led to the emergence of drug resistance in humans, animals, and agriculture, contributing to the global spread of this problem. Drug resistance can be either innate or acquired, with acquired resistance involving changes in the bacterial chromosomes or transferable elements. Bacterial species employ various mechanisms of drug resistance, including modifying the antibiotic targets, inactivating the drug, reducing uptake or increasing efflux, overexpressing the target, utilizing alternative pathways, and forming biofilms. One significant concern in the realm of drug resistance revolves around the emergence and proliferation of extended-spectrum beta-lactamases (ESBLs), a gene that is found in most gram-negative bacteria, primarily carried by Escherichia coli and Klebsiella pneumoniae in healthcare settings. ESBL-mediated resistance poses challenges for diagnosis, treatment, infection control, and antibiotic stewardship. Accurate detection of ESBL genes is crucial, and phenotypic methods are commonly used for initial screening. However, these methods have limitations, and confirmatory molecular techniques such as PCR and DNA sequencing are employed to accurately identify ESBL genes. Despite the significant global concerns surrounding ESBLs, they have spread worldwide, mainly facilitated by healthcare settings, inappropriate antimicrobial use, and host susceptibility. Addressing this issue requires implementing comprehensive measures, including enhanced surveillance, strict infection control practices, antibiotic stewardship programs, rapid diagnostic methods, alternative therapies, public education initiatives, and research focused on developing new drugs. Furthermore, collaboration among the healthcare, public health, and research sectors is pivotal in effectively combating the escalating threat posed by ESBL-mediated resistance. Antibiotics have revolutionized medical care by effectively treating bacterial infections. However, the emergence of ESBL gene resistance poses a global challenge that requires an integrated approach to prevent a threatening future.202438700878
6607150.9977The Growing Threat of Antibiotic Resistance in Children. Antimicrobial resistance is a global public health threat and a danger that continues to escalate. These menacing bacteria are having an impact on all populations; however, until recently, the increasing trend in drug-resistant infections in infants and children has gone relatively unrecognized. This article highlights the current clinical and molecular data regarding infection with antibiotic-resistant bacteria in children, with an emphasis on transmissible resistance and spread via horizontal gene transfer.201829406971
6672160.9977Antibiotic 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
4868170.9976Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria. Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.201322667455
6617180.9976Mechanisms in colistin-resistant superbugs transmissible from veterinary, livestock and animal food products to humans. In the era of antibiotic resistance, where multidrug-resistant (MDR), extensively drug resistant (XDR), and pan-drug resistant (PDR) Gram-negative infections are prevalent, it is crucial to identify the primary sources of antibiotic resistance, understand resistant mechanisms, and develop strategies to combat these mechanisms. The emergence of resistance to last-resort antibiotics like colistin has sparked a war between humanity and resistant bacteria, leaving humanity struggling to find effective countermeasures. Although colistin is used as a highly toxic antibiotic in infections that are not treated with routine antibiotics, its widespread use in animal breeding and veterinary medicine has contributed to the spread of colistin-resistant bacteria, plasmid-borne colistin resistance genes (mcr), and antibiotic residues in livestock and animal-derived foods. These sources can potentially transmit colistin resistance to humans through various routes. Therefore, managing the use of colistin in livestock and animal foods, implementing strict monitoring, and establishing guidelines for its proper use are essential to prevent the escalation of colistin resistance. This review article discusses the latest mechanisms of colistin antibiotic resistance, particularly biofilm production as a public health threat, the livestock and animal food sources of this resistance, and the routes of transmission to humans.202540386099
6610190.9976The Gut Microbiome and Colistin Resistance: A Hidden Driver of Antimicrobial Failure. Colistin, a polymyxin antibiotic reintroduced as a last-resort therapy against multidrug-resistant Gram-negative bacteria, is increasingly being compromised by the emergence of plasmid-mediated colistin resistance genes (mcr-1 to mcr-10). The human gut microbiota serves as a major reservoir and transmission hub for these resistance determinants, even among individuals without prior colistin exposure. This review explores the mechanisms, dissemination, and clinical implications of mcr-mediated colistin resistance within the gut microbiota, highlighting its role in horizontal gene transfer, colonization, and environmental persistence. A comprehensive synthesis of the recent literature was conducted, focusing on epidemiological studies, molecular mechanisms, neonatal implications and decolonization strategies. The intestinal tract supports the enrichment and exchange of mcr genes among commensal and pathogenic bacteria, especially under antibiotic pressure. Colistin use in agriculture has amplified gut colonization with resistant strains in both animals and humans. Surveillance gaps remain, particularly in neonatal populations, where colonization may occur early and persist silently. Promising interventions, such as fecal microbiota transplantation and phage therapies, are under investigation but lack large-scale clinical validation. The gut microbiome plays a central role in the global spread of colistin resistance. Mitigating this threat requires integrated One Health responses, improved diagnostics for gut colonization, and investment in microbiome-based therapies. A proactive, multisectoral approach is essential to safeguard colistin efficacy and address the expanding threat of mcr-mediated resistance.202541009471