Quaternary ammonium disinfectants and antiseptics: tolerance, resistance and potential impact on antibiotic resistance. - Related Documents




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429001.0000Quaternary 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
429110.9999Reduced Susceptibility and Increased Resistance of Bacteria against Disinfectants: A Systematic Review. Disinfectants are used to reduce the concentration of pathogenic microorganisms to a safe level and help to prevent the transmission of infectious diseases. However, bacteria have a tremendous ability to respond to chemical stress caused by biocides, where overuse and improper use of disinfectants can be reflected in a reduced susceptibility of microorganisms. This review aims to describe whether mutations and thus decreased susceptibility to disinfectants occur in bacteria during disinfectant exposure. A systematic literature review following PRISMA guidelines was conducted with the databases PubMed, Science Direct and Web of Science. For the final analysis, 28 sources that remained of interest were included. Articles describing reduced susceptibility or the resistance of bacteria against seven different disinfectants were identified. The important deviation of the minimum inhibitory concentration was observed in multiple studies for disinfectants based on triclosan and chlorhexidine. A reduced susceptibility to disinfectants and potentially related problems with antibiotic resistance in clinically important bacterial strains are increasing. Since the use of disinfectants in the community is rising, it is clear that reasonable use of available and effective disinfectants is needed. It is necessary to develop and adopt strategies to control disinfectant resistance.202134946151
429220.9998The impact of different antibiotic regimens on the emergence of antimicrobial-resistant bacteria. BACKGROUND: The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address. METHODS/PRINCIPAL FINDINGS: A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains. CONCLUSIONS/SIGNIFICANCE: The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.200819112501
407530.9998Antimicrobial resistance in foodborne pathogens--a cause for concern? The widespread use of antibiotics in food animal production systems has resulted in the emergence of antibiotic resistant zoonotic bacteria that can be transmitted to humans through the food chain. Infection with antibiotic resistant bacteria negatively impacts on public health, due to an increased incidence of treatment failure and severity of disease. Development of resistant bacteria in food animals can result from chromosomal mutations but is more commonly associated with the horizontal transfer of resistance determinants borne on mobile genetic elements. Food may represent a dynamic environment for the continuing transfer of antibiotic resistance determinants between bacteria. Current food preservation systems that use a combination of environmental stresses to reduce growth of bacteria, may serve to escalate development and dissemination of antibiotic resistance among food related pathogens. The increasing reliance on biocides for pathogen control in food production and processing, heightens the risk of selection of biocide-resistant strains. Of particular concern is the potential for sublethal exposure to biocides to select for bacteria with enhanced multi-drug efflux pump activity capable of providing both resistance to biocides and cross-resistance to multiple antibiotics. Although present evidence suggests that biocide resistance is associated with a physiological cost, the possibility of the development of adaptive mutations conferring increased fitness cannot be ruled-out. Strategies aimed at inhibiting efflux pumps and eliminating plasmids could help to restore therapeutic efficacy to antibiotics and reduce the spread of antibiotic resistant foodborne pathogens through the food chain.200818781926
429340.9998Resistance to ocular antibiotics: an overview. The introduction of new antibiotic compounds into therapy initiates the development of resistance by the target bacteria. Resistance increases the risk of treatment failure with potentially serious consequences. Local application of antibacterial compounds to the eyes may lead to bacterial resistance in bacterial isolates from the eyes. The incidence of resistant strains of common pathogens is probably increasing. As compounds can be absorbed into the systemic circulation following ocular administration, the subsequent low concentrations in the blood could provide the selective pressure for the survival of resistant bacteria in the body. Despite this possibility, there are no reports of systemic resistance in bacteria following ocular administration of antibacterial compounds. All health-care professionals should be concerned about this possibility and continue to use these important compounds with respect.200717535364
429450.9998Anaerobic infections: update on treatment considerations. Anaerobic bacteria are the predominant indigenous flora of humans and, as a result, play an important role in infections, some of which are serious with a high mortality rate. These opportunistic pathogens are frequently missed in cultures of clinical samples because of shortcomings in collection and transport procedures as well as lack of isolation and susceptibility testing of anaerobes in many clinical microbiology laboratories. Correlation of clinical failures with known antibacterial resistance of anaerobic bacteria is seldom possible. Changes in resistance over time, and the discovery and characterization of resistance determinants in anaerobic bacteria, has increased recognition of problems in empirical treatment and has even resulted in changes in treatment guidelines. This review discusses the role of anaerobic bacteria in the normal flora of humans, their involvement in different mixed infections, developments in antibacterial resistance of the most frequent anaerobic pathogens and possible new treatment options.201020426496
429560.9998Antibiotic resistance in the intensive care unit. The increase in antibiotic resistance over the past 10 years can be traced to several factors. This includes exogenous transmission of bacteria, usually by hospital personnel. The use of potent antibiotics also can select for resistant bacteria initially present in low quantities. Strategies to reduce antibiotic resistance can be tailored to specific outbreaks in a given ICU. General strategies for reducing antibiotic resistance, on the other hand, include varying the agents used in the ICU over time. Reduction of the duration of therapy may prove to be another method of reducing antibiotic resistance.200212357111
423870.9998Biocide 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
407680.9998Overuse of food-grade disinfectants threatens a global spread of antimicrobial-resistant bacteria. Food-grade disinfectants are extensively used for microbial decontamination of food processing equipment. In recent years, food-grade disinfectants have been increasingly used. However, the overuse of disinfectants causes another major issue, which is the emergence and spread of antimicrobial-resistant bacteria on a global scale. As the ongoing pandemic takes global attention, bacterial infections with antibiotic resistance are another ongoing pandemic that often goes unnoticed and will be the next real threat to humankind. Here, the effects of food-grade disinfectant overuse on the global emergence and spread of antimicrobial-resistant bacteria were reviewed. It was found that longtime exposure to the most common food-grade disinfectants promoted resistance to clinically important antibiotics in pathogenic bacteria, namely cross-resistance. Currently, the use of disinfectants is largely unregulated. The mechanisms of cross-resistance are regulated by intrinsic molecular mechanisms including efflux pumps, DNA repair system, modification of the molecular target, and metabolic adaptation. Cross-resistance can also be acquired by mobile genetic elements. Long-term exposure to disinfectants has an impact on the dissemination of antimicrobial resistance in soil, plants, animals, water, and human gut environments.202436756870
943290.9998Disinfectants 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
4068100.9998Co-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
4240110.9998Genetics of antimicrobial resistance. Antimicrobial resistant strains of bacteria are an increasing threat to animal and human health. Resistance mechanisms to circumvent the toxic action of antimicrobials have been identified and described for all known antimicrobials currently available for clinical use in human and veterinary medicine. Acquired bacterial antibiotic resistance can result from the mutation of normal cellular genes, the acquisition of foreign resistance genes, or a combination of these two mechanisms. The most common resistance mechanisms employed by bacteria include enzymatic degradation or alteration of the antimicrobial, mutation in the antimicrobial target site, decreased cell wall permeability to antimicrobials, and active efflux of the antimicrobial across the cell membrane. The spread of mobile genetic elements such as plasmids, transposons, and integrons has greatly contributed to the rapid dissemination of antimicrobial resistance among several bacterial genera of human and veterinary importance. Antimicrobial resistance genes have been shown to accumulate on mobile elements, leading to a situation where multidrug resistance phenotypes can be transferred to a susceptible recipient via a single genetic event. The increasing prevalence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. The versatility with which bacteria adapt to their environment and exchange DNA between different genera highlights the need to implement effective antimicrobial stewardship and infection control programs in both human and veterinary medicine.200617127523
4067120.9998Metal Resistance and Its Association With Antibiotic Resistance. Antibiotic resistance is recognised as a major global threat to public health by the World Health Organization. Currently, several hundred thousand deaths yearly can be attributed to infections with antibiotic-resistant bacteria. The major driver for the development of antibiotic resistance is considered to be the use, misuse and overuse of antibiotics in humans and animals. Nonantibiotic compounds, such as antibacterial biocides and metals, may also contribute to the promotion of antibiotic resistance through co-selection. This may occur when resistance genes to both antibiotics and metals/biocides are co-located together in the same cell (co-resistance), or a single resistance mechanism (e.g. an efflux pump) confers resistance to both antibiotics and biocides/metals (cross-resistance), leading to co-selection of bacterial strains, or mobile genetic elements that they carry. Here, we review antimicrobial metal resistance in the context of the antibiotic resistance problem, discuss co-selection, and highlight critical knowledge gaps in our understanding.201728528649
9575130.9998Antibiotic resistome of Salmonella typhi: molecular determinants for the emergence of drug resistance. Resistome is a cluster of microbial genes encoding proteins with necessary functions to resist the action of antibiotics. Resistome governs essential and separate biological functions to develop resistance against antibiotics. The widespread clinical and nonclinical uses of antibiotics over the years have combined to select antibiotic-resistant determinants and develop resistome in bacteria. At present, the emergence of drug resistance because of resistome is a significant problem faced by clinicians for the treatment of Salmonella infection. Antibiotic resistome is a dynamic and ever-expanding component in Salmonella. The foundation of resistome in Salmonella is laid long before; therefore, the antibiotic resistome of Salmonella is reviewed, discussed, and summarized. We have searched the literature using PubMed, MEDLINE, and Google Scholar with related key terms (resistome, Salmonella, antibiotics, drug resistance) and prepared this review. In this review, we summarize the status of resistance against antibiotics in S. typhi, highlight the seminal work in the resistome of S. typhi and the genes involved in the antibiotic resistance, and discuss the various methods to identify S. typhi resistome for the proactive identification of this infection and quick diagnosis of the disease.202134085183
4060140.9998Current status of antibiotic resistance in animal production. It is generally accepted that the more antibiotics we use, the faster bacteria will develop resistance. Further it has been more or less accepted that once an antibiotic is withdrawn from the clinic, the resistance genes will eventually disappear, [table: see text] since they will no more be of any survival value for the bacterial cell. However, recent research has shown that after a long time period of exposure to antibiotics, certain bacterial species may adapt to this environment in such a way that they keep their resistance genes stably also after the removal of antibiotics. Thus, there is reason to believe that once resistance has developed it will not even in the long term be eradicated. What then can we do not to increase further the already high level of antibiotic-resistant bacteria in animals? We should of course encourage a prudent use of these valuable drugs. In Sweden antibiotics are not used for growth promoting purposes and are available only after veterinary prescription on strict indications. Generally, antimicrobial treatment of animals on individual or on herd basis should not be considered unless in connection with relevant diagnostics. The amounts of antibiotics used and the development of resistance in important pathogens should be closely monitored. Furthermore, resistance monitoring in certain non-pathogenic intestinal bacteria, which may serve as a reservoir for resistance genes is probably more important than hitherto anticipated. Once the usage of or resistance to a certain antibiotic seems to increase in an alarming way, steps should be taken to limit the usage of the drug in order to prevent further spread of resistance genes in animals, humans and the environment. Better methods for detecting and quantifying antibiotic resistance have to be developed. Screening methods must be standardized and evaluated in order to obtain comparable and reliable results from different countries. The genetic mechanisms for development of resistance and spread of resistance genes should be studied in detail. Research in these areas will lead to new ideas on how to inhibit the resistance mechanisms. So far, it has been well established that a heavy antimicrobial drug selective pressure in overcrowded populations of production animals creates favourable environments both for the emergence and the spread of antibiotic resistance genes.199910783714
4234150.9998Progress on mechanisms of antibiotic resistance in Clostridioides difficile. Clostridioides difficile (CD) is one of the most common pathogens causing health-care-associated infectious diarrhea and is listed by the U.S. Centers for Disease Control and Prevention as an urgent antibiotic resistance (AR) threat. Many resistance genes can be transferred between different CD strains present in the clinical setting, community, and environment. The antimicrobial resistance (AMR) of CD continues to evolve with the emergence and acquisition of new drug resistance mechanisms. CD has developed diverse drug resistance mechanisms, such as drug alteration, modification of the target site, and extrusion of drugs via efflux pumps. Researches have provided comprehensive knowledge about resistance mechanisms of macrolides and quinolones in CD. However, the mechanisms of resistance for metronidazole, vancomycin, and other therapeutic antibiotics against Clostridioides difficile infection (CDI) are only beginning to be elucidated. Some previously unfound mechanisms, such as plasmid-mediated drug resistance in CD, may also play an important role. In this review, we summarize the research progress on drug resistance mechanisms of CD with antimicrobial drugs already used clinically, such as metronidazole, vancomycin, and fidaxomicin, thereby providing the references for the clinical treatment and prevention of CDI, as well as the development of new antibacterial drugs and detection kits for drug resistant bacteria.202338764268
9438160.9998The challenge of antibiotic resistance: need to contemplate. "Survival of the fittest " holds good for men and animals as also for bacteria. A majority of bacteria in nature are nonpathogenic, a large number of them, live as commensals on our body leading a symbiotic existence. A limited population of bacteria which has became pathogenic was also sensitive to antibiotics to begin with. It is the man made antibiotic pressure, which has led to the emergence and spread of resistant genes amongst bacteria. Despite the availability of a large arsenal of antibiotics, the ability of bacteria to become resistant to antibacterial agents is amazing. This is more evident in the hospital settings where the antibiotic usage is maximum. The use of antibiotics is widespread in clinical medicine, agriculture, aquaculture, veterinary practice, poultry and even in household products. The major reason for this is the inappropriate use of antibiotics due to a lack of uniform policy and disregard to hospital infection control practices. The antibiotic cover provided by newer antibiotics has been an important factor responsible for the emergence of multi-drug resistant bacteria. Bacterial infections increase the morbidity and mortality, increase the cost of treatment, and prolong hospital stay adding to the economical burden on the nation. The problem is further compounded by the lack of education and " over the counter " availability of antibiotics in developing countries. Antibiotic resistance is now all pervasive with the developed world as much vulnerable to the problem. Despite advancement in medical technology for diagnosis and patient care, a person can still die of an infection caused by a multi-drug resistant bacteria. It is time to think, plan and formulate a strong antibiotic policy to address the burgeoning hospital infection.200515756040
4077170.9998Antimicrobial 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
4057180.9998A model of the transmission of antibiotic-resistant bacteria in the intensive care unit. Antibiotic resistance is a growing problem, affecting microorganisms found both in hospitals and in the community. In most patients, resistant organisms arise by transmission of already resistant microorganisms from another person, rather than arising by mutation in the index patient. Antibiotic resistance genes are often borne on plasmids or transposons on which they may be spread rapidly to other organisms in the same species or in other species. Plasmids and transposons readily pick up genes for resistance to other antibiotics or nonantibiotic agents ("linked resistance"). Control of the spread of antibiotic resistance may require limitation of the usage of other agents with linked resistance as well as of the antibiotics of primary interest. A model is described for the analysis of the transmission of antibiotic-resistant enteric bacteria in the ICU. The model deals with the baseline level of antibiotic resistance in the "source" patient, the effect of antibiotics in augmenting the concentration of resistant organisms in that patient, the role of patient-to-patient contact, and factors which may influence the "colonizability" of the recipient patient. Possible measures to reduce the spread of antibiotic resistance are discussed. It is hoped that the model may serve to focus discussion on some key ingredients of the transmission cycle.19968856750
4391190.9998'To be, or not to be'-The dilemma of 'silent' antimicrobial resistance genes in bacteria. Antimicrobial resistance is a serious threat to public health that dramatically undermines our ability to treat bacterial infections. Microorganisms exhibit resistance to different drug classes by acquiring resistance determinants through multiple mechanisms including horizontal gene transfer. The presence of drug resistance genotypes is mostly associated with corresponding phenotypic resistance against the particular antibiotic. However, bacterial communities harbouring silent antimicrobial resistance genes-genes whose presence is not associated with a corresponding resistant phenotype do exist. Under suitable conditions, the expression pattern of such genes often revert and regain resistance and could potentially lead to therapeutic failure. We often miss the presence of silent genes, since the current experimental paradigms are focused on resistant strains. Therefore, the knowledge on the prevalence, importance and mechanism of silent antibiotic resistance genes in bacterial pathogens are very limited. Silent genes, therefore, provide an additional level of complexity in the war against drug-resistant bacteria, reminding us that not only phenotypically resistant strains but also susceptible strains should be carefully investigated. In this review, we discuss the presence of silent antimicrobial resistance genes in bacteria, their relevance and their importance in public health.202235882476