Does the wide use of quaternary ammonium compounds enhance the selection and spread of antimicrobial resistance and thus threaten our health? - Related Documents




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951501.0000Does the wide use of quaternary ammonium compounds enhance the selection and spread of antimicrobial resistance and thus threaten our health? Quaternary ammonium compounds (QACs) are widely used biocides that possess antimicrobial effect against a broad range of microorganisms. These compounds are used for numerous industrial purposes, water treatment, antifungal treatment in horticulture, as well as in pharmaceutical and everyday consumer products as preserving agents, foam boosters, and detergents. Resistance toward QACs is widespread among a diverse range of microorganisms and is facilitated by several mechanisms such as modifications in the membrane composition, expression of stress response and repair systems, or expression of efflux pump genes. Development of resistance in both pathogenic and nonpathogenic bacteria has been related to application in human medicine and the food industry. QACs in cosmetic products will inevitably come into intimate contact with the skin or mucosal linings in the mouth and thus are likely to add to the selection pressure toward more QAC-resistant microorganisms among the skin or mouth flora. There is increasing evidence of coresistance and cross-resistance between QACs and a range of other clinically important antibiotics and disinfectants. Use of QACs may have driven the fixation and spread of certain resistance cassette collectors (class 1 integrons), currently responsible for a major part of antimicrobial resistance in gram-negative bacteria. More indiscriminate use of QACs such as in cosmetic products may drive the selection of further new genetic elements that will aid in the persistence and spread of antimicrobial resistance and thus in limiting our treatment options for microbial infections.201020370507
951410.9999Quaternary Ammonium Compounds: An Antimicrobial Mainstay and Platform for Innovation to Address Bacterial Resistance. Quaternary ammonium compounds (QACs) have represented one of the most visible and effective classes of disinfectants for nearly a century. With simple preparation, wide structural variety, and versatile incorporation into consumer products, there have been manifold developments and applications of these structures. Generally operating via disruption of one of the most fundamental structures in bacteria-the cell membrane-leading to cell lysis and bacterial death, the QACs were once thought to be impervious to resistance. Developments over the past decades, however, have shown this to be far from the truth. It is now known that a large family of bacterial genes (generally termed qac genes) encode efflux pumps capable of expelling many QAC structures from bacterial cells, leading to a decrease in susceptibility to QACs; methods of regulation of qac transcription are also understood. Importantly, qac genes can be horizontally transferred via plasmids to other bacteria and are often transmitted alongside other antibiotic-resistant genes; this dual threat represents a significant danger to human health. In this review, both QAC development and QAC resistance are documented, and possible strategies for addressing and overcoming QAC-resistant bacteria are discussed.201527622819
428220.9998Efflux Pump Inhibitors in Controlling Antibiotic Resistance: Outlook under a Heavy Metal Contamination Context. Multi-drug resistance to antibiotics represents a growing challenge in treating infectious diseases. Outside the hospital, bacteria with the multi-drug resistance (MDR) phenotype have an increased prevalence in anthropized environments, thus implying that chemical stresses, such as metals, hydrocarbons, organic compounds, etc., are the source of such resistance. There is a developing hypothesis regarding the role of metal contamination in terrestrial and aquatic environments as a selective agent in the proliferation of antibiotic resistance caused by the co-selection of antibiotic and metal resistance genes carried by transmissible plasmids and/or associated with transposons. Efflux pumps are also known to be involved in either antibiotic or metal resistance. In order to deal with these situations, microorganisms use an effective strategy that includes a range of expressions based on biochemical and genetic mechanisms. The data from numerous studies suggest that heavy metal contamination could affect the dissemination of antibiotic-resistant genes. Environmental pollution caused by anthropogenic activities could lead to mutagenesis based on the synergy between antibiotic efficacy and the acquired resistance mechanism under stressors. Moreover, the acquired resistance includes plasmid-encoded specific efflux pumps. Soil microbiomes have been reported as reservoirs of resistance genes that are available for exchange with pathogenic bacteria. Importantly, metal-contaminated soil is a selective agent that proliferates antibiotic resistance through efflux pumps. Thus, the use of multi-drug efflux pump inhibitors (EPIs) originating from natural plants or synthetic compounds is a promising approach for restoring the efficacy of existing antibiotics, even though they face a lot of challenges.202337049674
423830.9998Biocide tolerance in bacteria. Biocides have been employed for centuries, so today a wide range of compounds showing different levels of antimicrobial activity have become available. At the present time, understanding the mechanisms of action of biocides has also become an important issue with the emergence of bacterial tolerance to biocides and the suggestion that biocide and antibiotic resistance in bacteria might be linked. While most of the mechanisms providing antibiotic resistance are agent specific, providing resistance to a single antimicrobial or class of antimicrobial, there are currently numerous examples of efflux systems that accommodate and, thus, provide tolerance to a broad range of structurally unrelated antimicrobials, both antibiotics and biocides. If biocide tolerance becomes increasingly common and it is linked to antibiotic resistance, not only resistant (even multi-resistant) bacteria could be passed along the food chain, but also there are resistance determinants that can spread and lead to the emergence of new resistant microorganisms, which can only be detected and monitored when the building blocks of resistance traits are understood on the molecular level. This review summarizes the main advances reached in understanding the mechanism of action of biocides, the mechanisms of bacterial resistance to both biocides and antibiotics, and the incidence of biocide tolerance in bacteria of concern to human health and the food industry.201323340387
943240.9998Disinfectants and antiseptics: mechanisms of action and resistance. Chemical biocides are used for the prevention and control of infection in health care, targeted home hygiene or controlling microbial contamination for various industrial processes including but not limited to food, water and petroleum. However, their use has substantially increased since the implementation of programmes to control outbreaks of methicillin-resistant Staphylococcus aureus, Clostridioides difficile and severe acute respiratory syndrome coronavirus 2. Biocides interact with multiple targets on the bacterial cells. The number of targets affected and the severity of damage will result in an irreversible bactericidal effect or a reversible bacteriostatic one. Most biocides primarily target the cytoplasmic membrane and enzymes, although the specific bactericidal mechanisms vary among different biocide chemistries. Inappropriate usage or low concentrations of a biocide may act as a stressor while not killing bacterial pathogens, potentially leading to antimicrobial resistance. Biocides can also promote the transfer of antimicrobial resistance genes. In this Review, we explore our current understanding of the mechanisms of action of biocides, the bacterial resistance mechanisms encompassing both intrinsic and acquired resistance and the influence of bacterial biofilms on resistance. We also consider the impact of bacteria that survive biocide exposure in environmental and clinical contexts.202437648789
943750.9998Bacterial resistance to Quaternary Ammonium Compounds (QAC) disinfectants. Control of bacterial diseases has, for many years, been dependent on the use of antibiotics. Due to the high levels of efficacy of antibiotics in the past other disease control options have, to a large extent, been neglected. Mankind is now facing an increasing problem with antibiotic resistance. In an effort to retain some antibiotics for human use, there are moves afoot to limit or even ban the use of antibiotics in animal production. The use of antibiotics as growth promoters have been banned in the European Union and the USA. The potential ban on the use of antibiotics to treat diseases in production animals creates a dilemma for man-suffer significant problem with bacterial infection or suffer from a severe shortage of food! There are other options for the control of bacterial diseases. These include vaccine development, bacteriophage therapy, and improved biosecurity. Vaccine development against bacterial pathogens, particularly opportunistic pathogens, is often very challenging, as in many cases the molecular basis of the virulence is not always clearly understood. This is particularly true for Escherichia coli. Biosecurity (disinfection) has been a highly neglected area in disease control. With the ever-increasing problems with antibiotic resistance-the focus should return to improvements in biosecurity. As with antibiotics, bacteria also have mechanisms for resistance to disinfectants. To ensure that we do not replace one set of problems (increasing antibiotic resistance) with another (increasing resistance to disinfectants) we need to fully understand the modes of action of disinfectants and how the bacteria develop resistance to these disinfectants. Molecular studies have been undertaken to relate the presence of QAC resistance genes in bacteria to their levels of sensitivity to different generations of QAC-based products. The mode of action of QAC on bacteria has been studied using NanoSAM technology, where it was revealed that the QAC causes disruption of the bacterial cell wall and leaking of the cytoplasm out of the cells. Our main focus is on the control of bacterial and viral diseases in the poultry industry in a post-antibiotic era, but the principles remain similar for disease control in any veterinary field as well as in human medicine.201424595606
950960.9998Efflux-mediated tolerance to cationic biocides, a cause for concern? AbstractWith an increase in the number of isolates resistant to multiple antibiotics, infection control has become increasingly important to help combat the spread of multi-drug-resistant pathogens. An important component of this is through the use of disinfectants and antiseptics (biocides). Antibiotic resistance has been well studied in bacteria, but little is known about potential biocide resistance genes and there have been few reported outbreaks in hospitals resulting from a breakdown in biocide effectiveness. Development of increased tolerance to biocides has been thought to be more difficult due to the mode of action of biocides which affect multiple cellular targets compared with antibiotics. Very few genes which contribute towards increased biocide tolerance have been identified. However, the majority of those that have are components or regulators of different efflux pumps or genes which modulate membrane function/modification. This review will examine the role of efflux in increased tolerance towards biocides, focusing on cationic biocides and heavy metals against Gram-negative bacteria. As many efflux pumps which are upregulated by biocide presence also contribute towards an antimicrobial resistance phenotype, the role of these efflux pumps in cross-resistance to both other biocides and antibiotics will be explored.202236748532
954470.9998Nano-Strategies to Fight Multidrug Resistant Bacteria-"A Battle of the Titans". Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are enzyme inactivation, decreased cell permeability, target protection, target overproduction, altered target site/enzyme, increased efflux due to over-expression of efflux pumps, among others. Other more complex phenotypes, such as biofilm formation and quorum sensing do not appear as a result of the exposure of bacteria to antibiotics although, it is known that biofilm formation can be induced by antibiotics. These phenotypes are related to tolerance to antibiotics in bacteria. Different strategies, such as the use of nanostructured materials, are being developed to overcome these and other types of resistance. Nanostructured materials can be used to convey antimicrobials, to assist in the delivery of novel drugs or ultimately, possess antimicrobial activity by themselves. Additionally, nanoparticles (e.g., metallic, organic, carbon nanotubes, etc.) may circumvent drug resistance mechanisms in bacteria and, associated with their antimicrobial potential, inhibit biofilm formation or other important processes. Other strategies, including the combined use of plant-based antimicrobials and nanoparticles to overcome toxicity issues, are also being investigated. Coupling nanoparticles and natural-based antimicrobials (or other repurposed compounds) to inhibit the activity of bacterial efflux pumps; formation of biofilms; interference of quorum sensing; and possibly plasmid curing, are just some of the strategies to combat multidrug resistant bacteria. However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this. In this review, we will summarize the current research on nanoparticles and other nanomaterials and how these are or can be applied in the future to fight multidrug resistant bacteria.201830013539
407780.9998Antimicrobial resistance and its association with tolerance to heavy metals in agriculture production. Antimicrobial resistance is a recognized public health challenge that since its emergence limits the therapeutic options available to veterinarians and clinicians alike, when treatment is warranted. This development is further compounded by the paucity of new antibiotics. The agri-food industry benefits from the availability of antimicrobial compounds for food-animal production and crop protection. Nonetheless, their improper use can result in the selection for bacteria that are phenotypically resistant to these compounds. Another class of agents used in agriculture includes various cationic metals that can be included in animal diets as nutritional supplements or spread on pastures to support crop growth and protection. Heavy metals, in particular, are giving rise to concerns among public health professionals, as they can persist in the environment remaining stable for prolonged periods. Moreover, bacteria can also exhibit resistance to these chemical elements and the genes encoding this phenotype can be physically localized to plasmids that may also contain one or more antimicrobial resistance-encoding gene(s). This paper reviews our current understanding of the role that bacteria play in expressing resistance to heavy metals. It will describe how heavy metals are used in agri-food production, and explore evidence available to link resistance to heavy metals and antimicrobial compounds. In addition, possible solutions to reduce the impact of heavy metal resistance are also discussed, including using organic minerals and reducing the level of trace minerals in animal feed rations.201728213031
406890.9998Co-selection for antibiotic resistance by environmental contaminants. The environment is increasingly recognised as a hotspot for the selection and dissemination of antibiotic resistant bacteria and antibiotic resistance genes. These can be selected for by antibiotics and non-antibiotic agents (such as metals and biocides), with the evidence to support this well established by observational and experimental studies. However, there is emerging evidence to suggest that plant protection products (such as herbicides), and non-antibiotic drugs (such as chemotherapeutic agents), can also co-select for antibiotic resistance. This review aims to provide an overview of four classes of non-antibiotic agents (metals, biocides, plant protection products, and non-antibiotic drugs) and how they may co-select for antibiotic resistance, with a particular focus on the environment. It also aims to identify key knowledge gaps that should be addressed in future work, to better understand these potential co-selective agents.202439843965
9549100.9998Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review. The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.202437907198
9682110.9998Effect of Probiotics on Host-Microbiota in Bacterial Infections. Diseases caused by bacteria cause millions of deaths every year. In addition, the problem of resistance to antibiotics is so serious that it threatens the achievements of modern medicine. This is a very important global problem as some bacteria can also develop persistence. Indeed, the persistence of pathogenic bacteria has evolved as a potent survival strategy to overcome host organisms' defense mechanisms. Additionally, chronic or persistent infections may be caused by persisters which could facilitate antibiotic resistance. Probiotics are considered good bacteria. It has been described that the modulation of gut microbiota by probiotics could have a great potential to counteract the deleterious impact and/or regulate gut microbiota after bacterial infection. Probiotics might provide health benefits through the inhibition of pathogen growth or the replacement of pathogenic bacteria. Bearing in mind that current strategies to avoid bacterial persistence and prevent antibiotic resistance are not effective, other strategies need to be assessed. We have carried out a comprehensive review, which included the reported literature between 2016 and 2021, highlighting the clinical trials that reported the probiotics' potential to regulate gut microbiota after bacterial infection and focusing in particular on the context of antibiotic resistance and persister cells.202236145418
9516120.9998Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants. The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics.201829412107
9425130.9998A review of the current evidence of fruit phenolic compounds as potential antimicrobials against pathogenic bacteria. Fruits are among the main natural sources of phenolic compounds (PC). These compounds exert important antioxidant properties primarily associated with the presence of hydroxyl groups in their molecular structure. Additionally, the antibacterial effects of fruit phenolic-rich extracts or individual PC commonly found in fruits have been an emerging research focus in recent years. This review discusses by first time the available literature regarding the inhibitory effects of fruit PC on pathogenic bacteria, including not only their direct effects on bacterial growth and survival, but also their effects on virulence factors and antibiotic resistance, as well as the possible mechanism underlying these inhibitory properties. The results of the retrieved studies show overall that the antibacterial effects of fruit PC vary with the target bacteria, type of PC and length of exposure to these compounds. The type of solvent and procedures used for extraction and fruit cultivar also seem to influence the antibacterial effects of phenolic-rich fruit extracts. Fruit PC have shown wide-spectrum antibacterial properties besides being effective antibiotic resistance modifying agents in pathogenic bacteria and these effects have shown to be associated with interruption of efflux pump expression/function. Furthermore, fruit PC can cause down regulation of a variety of genes associated with virulence features in pathogenic bacteria. Results of available studies indicate the depolarization and alteration of membrane fluidity as mechanisms underlying the inhibition of pathogenic bacteria by fruit PC. These data reveal fruit PC have potential antimicrobial properties, which should be rationally exploited in solutions to control pathogenic bacteria.201930917922
9686140.9998Selective pressures for public antibiotic resistance. The rapid increase of antibiotic-resistant pathogens is severely limiting our current treatment possibilities. An important subset of the resistance mechanisms conferring antibiotic resistance have public effects, allowing otherwise susceptible bacteria to also survive antibiotic treatment. As susceptible bacteria can survive treatment without bearing the metabolic cost of producing the resistance mechanism, there is potential to increase their relative frequency in the population and, as such, select against resistant bacteria. Multiple studies showed that this altered selection for resistance is dependent on various environmental and treatment parameters. In this review, we provide a comprehensive overview of their most important findings and describe the main factors impacting the selection for resistance. In-depth understanding of the driving forces behind selection can aid in the design and implementation of alternative treatments which limit the risk of resistance development.202539158370
9519150.9998A comprehensive review on pharmacology of efflux pumps and their inhibitors in antibiotic resistance. The potential for the build-up of resistance to a particular antibiotic endangers its therapeutic application over time. In recent decades, antibiotic resistance has become one of the most severe threats to public health. It can be attributed to the relentless and unchecked use of antibiotics in healthcare sectors, cell culture, animal husbandry, and agriculture. Some classic examples of resistance mechanisms employed by bacteria include developing antibiotic degrading enzymes, modifying target sites previously targeted by antibiotics, and developing efflux mechanisms. Studies have shown that while some efflux pumps selectively extrude certain antibiotics, others extrude a structurally diverse class of antibiotics. Such extrusion of a structurally diverse class of antibiotics gives rise to multi-drug resistant (MDR) bacteria. These mechanisms are observed in gram-positive and gram-negative bacteria alike. Therefore, efflux pumps find their place in the list of high-priority targets for the treatment of antibiotic-resistance in bacteria mediated by efflux. Studies showed a significant escalation in bacteria's susceptibility to a particular antibiotic drug when tested with an efflux pump inhibitor (EPI) compared to when it was tested with the antibiotic drug alone. This review discusses the pharmacology, current status, and the future of EPIs in antibiotic resistance.202133964293
4290160.9998Quaternary ammonium disinfectants and antiseptics: tolerance, resistance and potential impact on antibiotic resistance. BACKGROUND: Due to the substantial increase in the use of disinfectants containing quaternary ammonion compounds (QACs) in healthcare and community settings during the COVID-19 pandemic, there is increased concern that heavy use might cause bacteria to develop resistance to QACs or contribute to antibiotic resistance. The purpose of this review is to briefly discuss the mechanisms of QAC tolerance and resistance, laboratory-based evidence of tolerance and resistance, their occurrence in healthcare and other real-world settings, and the possible impact of QAC use on antibiotic resistance. METHODS: A literature search was conducted using the PubMed database. The search was limited to English language articles dealing with tolerance or resistance to QACs present in disinfectants or antiseptics, and potential impact on antibiotic resistance. The review covered the period from 2000 to mid-Jan 2023. RESULTS: Mechanisms of QAC tolerance or resistance include innate bacterial cell wall structure, changes in cell membrane structure and function, efflux pumps, biofilm formation, and QAC degradation. In vitro studies have helped elucidate how bacteria can develop tolerance or resistance to QACs and antibiotics. While relatively uncommon, multiple episodes of contaminated in-use disinfectants and antiseptics, which are often due to inappropriate use of products, have caused outbreaks of healthcare-associated infections. Several studies have identified a correlation between benzalkonium chloride (BAC) tolerance and clinically-defined antibiotic resistance. The occurrence of mobile genetic determinants carrying multiple genes that encode for QAC or antibiotic tolerance raises the concern that widespread QAC use might facilitate the emergence of antibiotic resistance. Despite some evidence from laboratory-based studies, there is insufficient evidence in real-world settings to conclude that frequent use of QAC disinfectants and antiseptics has promoted widespread emergence of antibiotic resistance. CONCLUSIONS: Laboratory studies have identified multiple mechanisms by which bacteria can develop tolerance or resistance to QACs and antibiotics. De novo development of tolerance or resistance in real-world settings is uncommon. Increased attention to proper use of disinfectants is needed to prevent contamination of QAC disinfectants. Additional research is needed to answer many questions and concerns related to use of QAC disinfectants and their potential impact on antibiotic resistance.202337055844
9456170.9998Antibiotic treatments and microbes in the gut. Antibiotic therapies are important in combating disease-causing microorganisms and maintaining host health. It is widely accepted that exposure of the gut microbiota to antibiotics can lead to decreased susceptibility and the development of multi-drug-resistant disease-causing organisms, which can be a major clinical problem. It is also important to consider that antibiotics not only target pathogenic bacteria in the gut, but also can have damaging effects on the ecology of commensal species. This can reduce intrinsic colonization resistance and contribute to problems with antibiotic resistance, including lateral transfer of resistance genes. Our knowledge of the impact of antibiotic treatment on the ecology of the normal microbiota has been increased by recent advances in molecular methods and use of in vitro model systems to investigate the impact of antibiotics on the biodiversity of gut populations and the spread of antibiotic resistance. These highlight the need for more detailed structural and functional information on the long-term antibiotic-associated alterations in the gut microbiome, and spread of antibiotic resistance genes. This will be crucial for the development of strategies, such as targeted therapeutics, probiotics, prebiotics and synbiotics, to prevent perturbations in the gut microbiota, the restoration of beneficial species and improvements in host health.201424471523
9517180.9998Better together-Salmonella biofilm-associated antibiotic resistance. Salmonella poses a serious threat to public health and socioeconomic development worldwide because of its foodborne pathogenicity and antimicrobial resistance. This biofilm-planktonic lifestyle enables Salmonella to interfere with the host and become resistant to drugs, conferring inherent tolerance to antibiotics. The complex biofilm structure makes bacteria tolerant to harsh conditions due to the diversity of physiological, biochemical, environmental, and molecular factors constituting resistance mechanisms. Here, we provide an overview of the mechanisms of Salmonella biofilm formation and antibiotic resistance, with an emphasis on less-studied molecular factors and in-depth analysis of the latest knowledge about upregulated drug-resistance-associated genes in bacterial aggregates. We classified and extensively discussed each group of these genes encoding transporters, outer membrane proteins, enzymes, multiple resistance, metabolism, and stress response-associated proteins. Finally, we highlighted the missing information and studies that need to be undertaken to understand biofilm features and contribute to eliminating antibiotic-resistant and health-threatening biofilms.202337401756
9479190.9998Bacterial antimicrobial metal ion resistance. Metals such as mercury, arsenic, copper and silver have been used in various forms as antimicrobials for thousands of years with until recently, little understanding of their mode of action. The discovery of antibiotics and new organic antimicrobial compounds during the twentieth century saw a general decline in the clinical use of antimicrobial metal compounds, with the exception of the rediscovery of the use of silver for burns treatments and niche uses for other metal compounds. Antibiotics and new antimicrobials were regarded as being safer for the patient and more effective than the metal-based compounds they supplanted. Bacterial metal ion resistances were first discovered in the second half of the twentieth century. The detailed mechanisms of resistance have now been characterized in a wide range of bacteria. As the use of antimicrobial metals is limited, it is legitimate to ask: are antimicrobial metal resistances in pathogenic and commensal bacteria important now? This review details the new, rediscovered and 'never went away' uses of antimicrobial metals; examines the prevalence and linkage of antimicrobial metal resistance genes to other antimicrobial resistance genes; and examines the evidence for horizontal transfer of these genes between bacteria. Finally, we discuss the possible implications of the widespread dissemination of these resistances on re-emergent uses of antimicrobial metals and how this could impact upon the antibiotic resistance problem.201525418738