Antimicrobial resistance, mechanisms and its clinical significance. - Related Documents




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943901.0000Antimicrobial resistance, mechanisms and its clinical significance. Antimicrobial agents play a key role in controlling and curing infectious disease. Soon after the discovery of the first antibiotic, the challenge of antibiotic resistance commenced. Antimicrobial agents use different mechanisms against bacteria to prevent their pathogenesis and they can be classified as bactericidal or bacteriostatic. Antibiotics are one of the antimicrobial agents which has several classes, each with different targets. Consequently, bacteria are endlessly using methods to overcome the effectivity of the antibiotics by using distinct types of mechanisms. Comprehending the mechanisms of resistance is vital for better understanding and to continue use of current antibiotics. Which also helps to formulate synthetic antimicrobials to overcome the current mechanism of resistance. Also, encourage in prudent use and misuse of antimicrobial agents. Thus, decline in treatment costs and in the rate of morbidity and mortality. This review will be concentrating on the mechanism of actions of several antibiotics and how bacteria develop resistance to them, as well as the method of acquiring the resistance in several bacteria and how can a strain be resistant to several types of antibiotics. This review also analyzes the prevalence, major clinical implications, clinical causes of antibiotic resistance. Further, it evaluates the global burden of antimicrobial resistance, identifies various challenges and strategies in addressing the issue. Finally, put forward certain recommendations to prevent the spread and reduce the rate of resistance growth.202032201008
943810.9999The 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
424320.9999Action and resistance mechanisms of antibiotics: A guide for clinicians. Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and "bypass" of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.201729109626
979430.9999Antibiotic resistance in developing countries. During the past decade there have been major changes in the susceptibility of bacteria that cause various infections. Resistance to anti-infective agents, including antibiotics, is worldwide, both in developed and developing countries. Almost all bacterial species can develop resistance to anti-infective agents and resistance can readily be transferred among bacteria by transmissible elements (plasmids). Measures to prevent the emergence of resistance must be implemented urgently. A multiplicity of factors drive antibiotic resistance and solutions require the collaboration of governmental agencies, pharmaceutical companies, healthcare providers and consumers. Knowledge of resistance patterns and of the ways by which resistance is overcome is vital to the future of antimicrobial chemotherapy.200111434528
424540.9999Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence. In recent years, we have seen antimicrobial resistance rapidly emerge at a global scale and spread from one country to the other faster than previously thought. Superbugs and multidrug-resistant bacteria are endemic in many parts of the world. There is no question that the widespread use, overuse, and misuse of antimicrobials during the last 80 years have been associated with the explosion of antimicrobial resistance. On the other hand, the molecular pathways behind the emergence of antimicrobial resistance in bacteria were present since ancient times. Some of these mechanisms are the ancestors of current resistance determinants. Evidently, there are plenty of putative resistance genes in the environment, however, we cannot yet predict which ones would be able to be expressed as phenotypes in pathogenic bacteria and cause clinical disease. In addition, in the presence of inhibitory and sub-inhibitory concentrations of antibiotics in natural habitats, one could assume that novel resistance mechanisms will arise against antimicrobial compounds. This review presents an overview of antimicrobial resistance mechanisms, and describes how these have evolved and how they continue to emerge. As antimicrobial strategies able to bypass the development of resistance are urgently needed, a better understanding of the critical factors that contribute to the persistence and spread of antimicrobial resistance may yield innovative perspectives on the design of such new therapeutic targets.202031659373
406450.9999Antimicrobial resistance. The development of antimicrobial drugs, and particularly of antibiotics, has played a considerable role in substantially reducing the morbidity and mortality rates of many infectious diseases. However, the fact that bacteria can develop resistance to antibiotics has produced a situation where antimicrobial agents are losing their effectiveness because of the spread and persistence of drug-resistant organisms. To combat this, more and more antibiotics with increased therapeutic and prophylactic action will need to be developed.This article is concerned with antibiotic resistance in bacteria which are pathogenic to man and animals. The historical background is given, as well as some information on the present situation and trends of antibiotic resistance to certain bacteria in different parts of the world. Considerable concern is raised over the use of antibiotics in man and animals. It is stated that antibiotic resistance in human pathogens is widely attributed to the "misuse" of antibiotics for treatment and prophylaxis in man and to the administration of antibiotics to animals for a variety of purposes (growth promotion, prophylaxis, or therapy), leading to the accumulation of resistant bacteria in their flora. Factors favouring the development of resistance are discussed.19836603914
968260.9999Effect 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
980570.9999Molecular mechanisms of multidrug resistance in clinically relevant enteropathogenic bacteria (Review). Multidrug resistant (MDR) enteropathogenic bacteria are a growing problem within the clinical environment due to their acquired tolerance to a wide range of antibiotics, thus causing severe illnesses and a tremendous economic impact in the healthcare sector. Due to its difficult treatment, knowledge and understanding of the molecular mechanisms that confer this resistance are needed. The aim of the present review is to describe the mechanisms of antibiotic resistance from a genomic perspective observed in bacteria, including naturally acquired resistance. The present review also discusses common pharmacological and alternative treatments used in cases of infection caused by MDR bacteria, thus covering necessary information for the development of novel antimicrobials and adjuvant molecules inhibiting bacterial proliferation.202236561977
943780.9999Bacterial 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
957690.9999Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century. With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.202134940513
9804100.9999Antimicrobial Peptides as an Alternative for the Eradication of Bacterial Biofilms of Multi-Drug Resistant Bacteria. Bacterial resistance is an emergency public health problem worldwide, compounded by the ability of bacteria to form biofilms, mainly in seriously ill hospitalized patients. The World Health Organization has published a list of priority bacteria that should be studied and, in turn, has encouraged the development of new drugs. Herein, we explain the importance of studying new molecules such as antimicrobial peptides (AMPs) with potential against multi-drug resistant (MDR) and extensively drug-resistant (XDR) bacteria and focus on the inhibition of biofilm formation. This review describes the main causes of antimicrobial resistance and biofilm formation, as well as the main and potential AMP applications against these bacteria. Our results suggest that the new biomacromolecules to be discovered and studied should focus on this group of dangerous and highly infectious bacteria. Alternative molecules such as AMPs could contribute to eradicating biofilm proliferation by MDR/XDR bacteria; this is a challenging undertaking with promising prospects.202235336016
9801110.9999Problems and changing patterns of resistance with gram-negative bacteria. Throughout the antibiotic era, the emergence of drug-resistant bacteria has paralleled the development of new antimicrobial agents. As a result of selection pressures and invasive techniques that prolong the lives of seriously ill hospital patients, gram-negative bacilli have become the dominant causes of nosocomial infection. These microorganisms produce a diversity of antibiotic-inactivating enzymes. Moreover, the cell envelope of gram-negative bacteria provides a series of barriers that keep antibiotics from reaching their targets. Resistance factors can be transmitted among bacteria of different genera and species, thus conferring multidrug resistance. These problems continue to challenge scientists to better understand resistance mechanisms and to develop new compounds to circumvent them.19853909311
9487120.9999Molecular mechanisms of antibiotic resistance revisited. Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the pipeline. Understanding the molecular mechanisms that bacteria use to resist the action of antimicrobials is critical to recognize global patterns of resistance and to improve the use of current drugs, as well as for the design of new drugs less susceptible to resistance development and novel strategies to combat resistance. In this Review, we explore recent advances in understanding how resistance genes contribute to the biology of the host, new structural details of relevant molecular events underpinning resistance, the identification of new resistance gene families and the interactions between different resistance mechanisms. Finally, we discuss how we can use this information to develop the next generation of antimicrobial therapies.202336411397
9443130.9999Is Genetic Mobilization Considered When Using Bacteriophages in Antimicrobial Therapy? The emergence of multi-drug resistant bacteria has undermined our capacity to control bacterial infectious diseases. Measures needed to tackle this problem include controlling the spread of antibiotic resistance, designing new antibiotics, and encouraging the use of alternative therapies. Phage therapy seems to be a feasible alternative to antibiotics, although there are still some concerns and legal issues to overcome before it can be implemented on a large scale. Here we highlight some of those concerns, especially those related to the ability of bacteriophages to transport bacterial DNA and, in particular, antibiotic resistance genes.201729206153
9488140.9999Minimizing potential resistance: the molecular view. The major contribution of molecular biology to the study of antibiotic resistance has been the elucidation of nearly all biochemical mechanisms of resistance and the routes for dissemination of genetic information among bacteria. In this review, we consider the potential contribution of molecular biology to counteracting the evolution of resistant bacteria. In particular, we emphasize the fact that fundamental approaches have had direct practical effects on minimizing potential resistance: by improving interpretation of resistance phenotypes, by providing more adequate human therapy, by fostering more prudent use of antibiotics, and by allowing the rational design of new drugs that evade existing resistance mechanisms or address unexploited targets.200111524711
4091150.9999Insights into novel antimicrobial compounds and antibiotic resistance genes from soil metagenomes. In recent years a major worldwide problem has arisen with regard to infectious diseases caused by resistant bacteria. Resistant pathogens are related to high mortality and also to enormous healthcare costs. In this field, cultured microorganisms have been commonly focused in attempts to isolate antibiotic resistance genes or to identify antimicrobial compounds. Although this strategy has been successful in many cases, most of the microbial diversity and related antimicrobial molecules have been completely lost. As an alternative, metagenomics has been used as a reliable approach to reveal the prospective reservoir of antimicrobial compounds and antibiotic resistance genes in the uncultured microbial community that inhabits a number of environments. In this context, this review will focus on resistance genes as well as on novel antibiotics revealed by a metagenomics approach from the soil environment. Biotechnology prospects are also discussed, opening new frontiers for antibiotic development.201425278933
9558160.9999Antimicrobial Resistance: Enzymes, Proteins, and Computational Resources. Antimicrobial resistance (AMR) is an important health concern rooted in antibiotic misuse and overuse, resulting in drug-resistant bacteria. However, resistance to these antimicrobials developed as soon as they were administered. Several variables lead to the progression of antimicrobial resistance (AMR), making it a multifaceted challenge for healthcare systems worldwide, such as erroneous diagnosis, inappropriate prescription, incomplete treatment, and many more. Getting an in-depth idea about the mechanism underlying AMR development is essential to overcome this. This review aims to provide information on how various enzymes or proteins aid in the antimicrobial resistance mechanisms and also highlight the clinical perspective of AMR, emphasizing its growing impact on patient outcomes, and incorporate the latest recent data from the World Health Organisation (WHO), underscoring the global urgency of the AMR crisis, with specific attention to trends observed in recent years. Additionally, it is intended to provide ideas about inhibitors that can inhibit the mechanism of antibiotic resistance and also to provide an idea about numerous computational resources available that can be employed to predict genes and/or proteins and enzymes involved in various antibiotic resistance mechanisms.202540770471
9562170.9999Fight against antimicrobial resistance. Antimicrobial and antibiotic resistance is ever increasing and the fight against it is a battle that can never be won. Nevertheless, some possibilities exist to improve this situation, at least in part. The present review article discusses some approaches that can be used to control microbial resistance. Possible strategies are (1) designing new vaccines against resistant bacterial strains; (2) investigation of the potential of both traditional and non-traditional sources of natural substances for use as new antibiotics; (3) search for genes specifying biosynthesis of antibiotics; (4) use of forgotten natural compounds and their transformation, and (5) investigation of new antibiotic targets in pathogenic bacteria. Particular attention is paid to the search for new compounds that would be able to inhibit pathogenic bacteria resistant to existing antibiotics.201830126284
9806180.9999Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches. The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.202032586045
4061190.9999Beyond serial passages: new methods for predicting the emergence of resistance to novel antibiotics. Market launching of a new antibiotic requires knowing in advance its benefits and possible risks, and among them how rapidly resistance will emerge and spread among bacterial pathogens. This information is not only useful from a public health point of view, but also for pharmaceutical industry, in order to reduce potential waste of resources in the development of a compound that might be discontinued at the short term because of resistance development. Most assays currently used for predicting the emergence of resistance are based on culturing the target bacteria by serial passages in the presence of increasing concentrations of antibiotics. Whereas these assays may be valuable for identifying mutations that might cause resistance, they are not useful to establish how fast resistance might appear, neither to address the risk of spread of resistance genes by horizontal gene transfer. In this article, we review recent information pertinent for a more accurate prediction on the emergence and dispersal of antibiotic resistance.201121835695