Mechanisms in colistin-resistant superbugs transmissible from veterinary, livestock and animal food products to humans. - Related Documents




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661701.0000Mechanisms 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
661610.9999The 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
487320.9999Farm animals and aquaculture: significant reservoirs of mobile colistin resistance genes. Colistin resistance has attracted substantial attention after colistin was considered as a last-resort drug for the treatment of infections caused by carbapenem-resistant and/or multidrug-resistant (MDR) Gram-negative bacteria in clinical settings. However, with the discovery of highly mobile colistin resistance (mcr) genes, colistin resistance has become an increasingly urgent issue worldwide. Despite many reviews, which summarized the prevalence, mechanisms, and structures of these genes in bacteria of human and animal origin, studies on the prevalence of mobile colistin resistance genes in aquaculture and their transmission between animals and humans remain scarce. Herein, we review recent reports on the prevalence of colistin resistance genes in animals, especially wildlife and aquaculture, and their possibility of transmission to humans via the food chain. This review also gives some insights into the routine surveillance, changing policy and replacement of polymyxins by polymyxin derivatives, molecular inhibitors, and traditional Chinese medicine to tackle colistin resistance.202032114703
433230.9999Development 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
487440.9999Mobilized colistin resistance (mcr) genes from 1 to 10: a comprehensive review. At the present time, the polymyxin antibiotic colistin is considered a last-line treatment option for severe human infections caused by multi-drug and carbapenem-resistant Gram-negative bacteria. Lately, the vast spread of colistin resistance among bacteria has got great attention worldwide due to its significant role as the last refuge in treating diseases caused by the resistant infectious agents. Therefore, the discovery of plasmid-mediated mobile colistin resistance (mcr) genes raised global public health concerns as they can spread by horizontal transfer and have chances of global dissemination. To date, ten slightly different variants of the mcr-1 gene (mcr-1 to mcr-10) have been identified in different bacteria isolated from animals, foods, farms, humans, and the environment. Therefore, the issue of mcr spread is growing and worsening day after day. In this backdrop, the current article presents an overview of mcr variants, their spread, and the resistance mechanisms they confer. Hence, this paper will advance our knowledge about colistin resistance while supporting the efforts toward better stewardship and proper usage of antimicrobials.202133839987
488850.9999A 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
487260.9999A Review on Colistin Resistance: An Antibiotic of Last Resort. Antibiotic resistance has emerged as a significant global public health issue, driven by the rapid adaptation of microorganisms to commonly prescribed antibiotics. Colistin, previously regarded as a last-resort antibiotic for treating infections caused by Gram-negative bacteria, is increasingly becoming resistant due to chromosomal mutations and the acquisition of resistance genes carried by plasmids, particularly the mcr genes. The mobile colistin resistance gene (mcr-1) was first discovered in E. coli from China in 2016. Since that time, studies have reported different variants of mcr genes ranging from mcr-1 to mcr-10, mainly in Enterobacteriaceae from various parts of the world, which is a major concern for public health. The co-presence of colistin-resistant genes with other antibiotic resistance determinants further complicates treatment strategies and underscores the urgent need for enhanced surveillance and antimicrobial stewardship efforts. Therefore, understanding the mechanisms driving colistin resistance and monitoring its global prevalence are essential steps in addressing the growing threat of antimicrobial resistance and preserving the efficacy of existing antibiotics. This review underscores the critical role of colistin as a last-choice antibiotic, elucidates the mechanisms of colistin resistance and the dissemination of resistant genes, explores the global prevalence of mcr genes, and evaluates the current detection methods for colistin-resistant bacteria. The objective is to shed light on these key aspects with strategies for combating the growing threat of resistance to antibiotics.202438674716
489070.9998Understanding of Colistin Usage in Food Animals and Available Detection Techniques: A Review. Progress in the medical profession is determined by the achievements and effectiveness of new antibiotics in the treatment of microbial infections. However, the development of multiple-drug resistance in numerous bacteria, especially Gram-negative bacteria, has limited the treatment options. Due to this resistance, the resurgence of cyclic polypeptide drugs like colistin remains the only option. The drug, colistin, is a well-known growth inhibitor of Gram-negative bacteria like Acinetobacter baumanni, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Technological advancements have uncovered the role of the mcr-1(mobilized colistin resistance) gene, which is responsible for the development of resistance in Gram-negative bacteria, which make them distinct from other bacteria without this gene. Additionally, food animals have been determined to be the reservoir for colistin resistance microbes, from which they spread to other hosts. Due to the adverse effects of colistin, many developed countries have prohibited its usage in animal foods, but developing countries are still using colistin in animal food production, thereby imposing a major risk to the public health. Therefore, there is a need for implementation of sustainable measures in livestock farms to prevent microbial infection. This review highlights the negative effects (increased resistance) of colistin consumption and emphasizes the different approaches used for detecting colistin in animal-based foods as well as the challenges associated with its detection.202033081121
661480.9998Whole-Genome Sequencing of Pathogenic Bacteria-New Insights into Antibiotic Resistance Spreading. In recent years, the acquisition of antimicrobial resistance (AMR) by both pathogenic and opportunistic bacteria has become a major problem worldwide, which was already noticed as a global healthcare threat by the World Health Organization [...].202134946225
433190.9998Infectious drug resistance. The emergence of antibiotic-resistant bacteria is a serious threat to public health. Infectious drug resistance, the transmission of resistant determinants from antibiotic-resistant bacteria to antibiotic-sensitive bacterial populations, creates clinical problems that must be addressed. Adequate knowledge of the mechanisms responsible for bacteria resistance is important for ensuring the benefits of antimicrobial therapy.19853981648
4185100.9998Containment of antimicrobial resistance due to use of antimicrobial agents in animals intended for food: WHO perspective. The use of antimicrobial agents in humans and food-producing animals has important consequences for human and animal health, as it can lead to the development of resistant bacteria (pathogens and/or commensals with resistance genes). Moreover, resistant bacteria in animals can be transferred to people--usually through the consumption of food, but also through direct contact with food-producing animals or through environmental spread. Ultimately, this can result in human infections with bacteria that are resistant to antimicrobial agents and that can therefore be difficult or impossible to cure. Of special concern is resistance to antimicrobial agents classified by the World Health Organization (WHO) as critically important for human medicine, such as fluoroquinolones, third- and fourth-generation cephalosporins, and macrolides. WHO encourages the agricultural, food, veterinary and health sectors to work together to eliminate the burden of antimicrobial resistance arising from the use of antimicrobial agents in food-producing animals. Joint efforts should be made to reduce the inappropriate use of antimicrobial agents (e.g. the use of antimicrobials as growth promoters) and limit the spread of bacteria resistant to antimicrobial agents. WHO will continueto address this issue in conjunction with the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health, the animal health/production industry and other important stakeholders. It will also continue to enhance the capacity of its Member States (through training courses and sentinel studies), particularly developing countries, to conduct integrated surveillance of antimicrobial use and resistance, to carry out risk assessments to support the selection of risk management options and to implement strategies for the containment of antimicrobial resistance.201222849282
6610110.9998The 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
4889120.9998The 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
4887130.9998Mechanisms 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
4330140.9998Decolonization of asymptomatic carriage of multi-drug resistant bacteria by bacteriophages? Antimicrobial resistance is a major threat to human and animal health and accounted for up to 4.5 million deaths worldwide in 2019. Asymptomatic colonization of the digestive tract by multidrug resistant (multi-resistant) bacteria such as extended-spectrum beta-lactamase-, or carbapenemase- producing Enterobacterales is (i) a risk factor for infection by these multi-resistant bacteria, (ii) a risk factor of dissemination of these multi-resistant bacteria among patients and in the community, and (iii) allows the exchange of resistance genes between bacteria. Hence, decolonization or reduction of the gastrointestinal tract colonization of these multi-resistant bacteria needs to be urgently explored. Developing new non-antibiotic strategies to limit or eradicate multi-resistant bacteria carriage without globally disrupting the microbiota is considered a priority to fight against antibiotic resistance. Probiotics or Fecal Microbiota Transplantation are alternative strategies to antibiotics that have been considered to decolonize intestinal tract from MDR bacteria but there is currently no evidence demonstrating their efficacy. Lytic bacteriophages are viruses that kill bacteria and therefore could be considered as a promising strategy to combat antibiotic resistance. Successful decolonization by bacteriophages has already been observed clinically. Here, we discuss the current alternative strategies considered to decolonize the digestive tract of multidrug resistant bacteria, briefly describing probiotics and fecal microbiota transplantation approaches, and then detail the in vivo and in vitro studies using bacteriophages, while discussing their limits regarding the animal models used, the characteristics of phages used and their activity in regards of the gut anatomy.202338075897
6631150.9998Antibiotic Resistance in Escherichia coli from Farm Livestock and Related Analytical Methods: A Review. The indiscriminate use of antibiotics for the treatment of human and animal infections has led to the rise of resistance in pathogens and in commensal bacteria. In particular, farm animals may act as vectors for the dissemination of drug-resistant genes because of the intensive use of antibiotics in animal production, enabling resistance to a wide range of antimicrobial agents, including those normally used in human medicine. Escherichia coli, being a widespread commensal, is considered a good indicator of antibiotic use. Ultimately, it is emerging as a global threat, developing dramatically high levels of antibiotic resistance to multiple classes of drugs. Its prevalence in food animals is hence alarming, and more studies are needed in order to ascertain the spread dynamics between the food chain and humans. In this context, great attention should be paid to the accurate detection of resistance by conventional and molecular methods. In this review, a comprehensive list of the most widely used testing methods is also addressed.201829554996
6673160.9998A brief multi-disciplinary review on antimicrobial resistance in medicine and its linkage to the global environmental microbiota. The discovery and introduction of antimicrobial agents to clinical medicine was one of the greatest medical triumphs of the 20th century that revolutionized the treatment of bacterial infections. However, the gradual emergence of populations of antimicrobial-resistant pathogenic bacteria resulting from use, misuse, and abuse of antimicrobials has today become a major global health concern. Antimicrobial resistance (AMR) genes have been suggested to originate from environmental bacteria, as clinically relevant resistance genes have been detected on the chromosome of environmental bacteria. As only a few new antimicrobials have been developed in the last decade, the further evolution of resistance poses a serious threat to public health. Urgent measures are required not only to minimize the use of antimicrobials for prophylactic and therapeutic purposes but also to look for alternative strategies for the control of bacterial infections. This review examines the global picture of antimicrobial resistance, factors that favor its spread, strategies, and limitations for its control and the need for continuous training of all stake-holders i.e., medical, veterinary, public health, and other relevant professionals as well as human consumers, in the appropriate use of antimicrobial drugs.201323675371
4871170.9998Colistin: from the shadows to a One Health approach for addressing antimicrobial resistance. Antimicrobial resistance (AMR) poses a serious threat to human, animal and environmental health worldwide. Colistin has regained importance as a last-resort treatment against multi-drug-resistant Gram-negative bacteria. However, colistin resistance has been reported in various Enterobacteriaceae species isolated from several sources. The 2015 discovery of the plasmid-mediated mcr-1 (mobile colistin resistance) gene conferring resistance to colistin was a major concern within the scientific community worldwide. The global spread of this plasmid - as well as the subsequent identification of 10 MCR-family genes and their variants that catalyse the addition of phosphoethanolamine to the phosphate group of lipid A - underscores the urgent need to regulate the use of colistin, particularly in animal production. This review traces the history of colistin resistance and mcr-like gene identification, and examines the impact of policy changes regarding the use of colistin on the prevalence of mcr-1-positive Escherichia coli and colistin-resistant E. coli from a One Health perspective. The withdrawal of colistin as a livestock growth promoter in several countries reduced the prevalence of colistin-resistant bacteria and its resistance determinants (e.g. mcr-1 gene) in farm animals, humans and the environment. This reduction was certainly favoured by the significant fitness cost associated with acquisition and expression of the mcr-1 gene in enterobacterial species. The success of this One Health intervention could be used to accelerate regulation of other important antimicrobials, especially those associated with bacterial resistance mechanisms linked to high fitness cost. The development of global collaborations and the implementation of sustainable solutions like the One Health approach are essential to manage AMR.202336640846
6618180.9998A review of antimicrobial resistance in imported foods. Antimicrobial resistance is one of the most serious threats to medical science. Food supply is recognized as a potential source of resistant bacteria, leading to the development of surveillance programs targeting primarily poultry, pork, and beef. These programs are limited in scope, not only in the commodities tested, but also in the organisms targeted (Escherichia coli, Salmonella, and Campylobacter); consequently, neither the breadth of food products available nor the organisms that may harbour clinically relevant and (or) mobile resistance genes are identified. Furthermore, there is an inadequate understanding of how international trade in food products contributes to the global dissemination of resistance. This is despite the recognized role of international travel in disseminating antimicrobial-resistant organisms, notably New Delhi metallo-beta-lactamase. An increasing number of studies describing antimicrobial-resistant organisms in a variety of imported foods are summarized in this review.202234570987
6612190.9998Carbapenem Resistance among Marine Bacteria-An Emerging Threat to the Global Health Sector. The emergence of antibiotic resistance among pathogenic microorganisms is a major issue for global public health, as it results in acute or chronic infections, debilitating diseases, and mortality. Of particular concern is the rapid and common spread of carbapenem resistance in healthcare settings. Carbapenems are a class of critical antibiotics reserved for treatment against multidrug-resistant microorganisms, and resistance to this antibiotic may result in limited treatment against infections. In addition to in clinical facilities, carbapenem resistance has also been identified in aquatic niches, including marine environments. Various carbapenem-resistant genes (CRGs) have been detected in different marine settings, with the majority of the genes incorporated in mobile genetic elements, i.e., transposons or plasmids, which may contribute to efficient genetic transfer. This review highlights the potential of the marine environment as a reservoir for carbapenem resistance and provides a general overview of CRG transmission among marine microbes.202134683467