Antibiotic resistance: how it arises, the current position and strategies for the future. - Related Documents




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979501.0000Antibiotic resistance: how it arises, the current position and strategies for the future. After 70 years of antibiotic therapy, the threat of untreatable infections is again a reality with resistance to antibiotics increasing in both Gram positive and Gram negative bacteria. Antibiotic-resistant bacteria cause both community and healthcare associated infections, presenting challenges in treatment and management. The development of new and novel antibiotics, particularly for Gram negative bacteria, is worryingly lacking. This article reviews the current situation and examines future strategies to tackle the continued threat of bacterial resistance.200919835196
980610.9999Resistance 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
433120.9999Infectious 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
432830.9999Bugs for the next century: the issue of antibiotic resistance. OBJECTIVE: To address the issue of emerging antibiotic resistance and examine which organisms will continue to pose problems in the new century. METHODS: Review of articles pertaining to bacteria recognised for increasing resistance. RESULTS: Changing resistance patterns are correlated with patterns of antibiotic use. This results in fewer effective drugs against "old" established bacteria e.g. gram-positives such as Streptococcus pneumoniae and Staphylococcus aureus. Resistance in gram-negative bacteria is also steadily increasing. Nosocomial gram-negative bacteria are capable of many different resistance mechanisms, often rendering them multiply-resistant. Antibiotic resistance results in morbidity and mortality from treatment failures and increased health care costs. CONCLUSION: Despite extensive research and enormous resources spent, the pace of drug development has not kept up with the development of resistance. As resistance spreads, involving more and more organisms, there is concern that we may be nearing the end of the antimicrobial era. Measures that can and should be taken to counter this threat of antimicrobial resistance include co-ordinated surveillance, rational antibiotic usage, better compliance with infection control and greater use of vaccines.200111379419
979440.9999Antibiotic 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
979650.9999Bacteriophage therapy to combat MDR non-fermenting Gram-negative bacteria causing nosocomial infections: recent progress and challenges. Clinicians face significant challenges in managing nosocomial infections, primarily due to antimicrobial resistance in multidrug-resistant bacteria. Regardless of the availability of a wide range of antimicrobials in the market, resistance is escalating rampantly with every passing day, which has become a global concern. Hence, it is essential to discover new and more efficient techniques to eliminate pathogens from healthcare settings. Along with eliminating pathogenic bacteria, mitigating their antimicrobial resistance with novel methods is very essential. Recently, bacteriophages have re-emerged as a promising therapeutic alternative to treat serious infections caused by bacterial pathogens. Bacteriophages were discovered for the first time a century ago, but their usage has recently regained more attention in treating bacterial pathogens. Bacteriophages also help in mitigating the worldwide problem of antibiotic resistance, particularly augmented by Gram-negative bacteria. This review discussed the advancements in the usage of bacteriophages in combating the antimicrobial resistance of multidrug-resistant Gram-negative bacteria, with a prime focus on Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cepacia complex (Bcc), which are renowned non-fermenting Gram-negative bacteria (NFGNB) pathogens. Additionally, the effects of single phage, phage cocktails, and combination therapy with antibiotics on bacterial biofilms and polymicrobial biofilms are also discussed.202540478338
980560.9999Molecular 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
943870.9999The 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
433280.9999Development 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
979790.9999Evaluation of Antibiotic Resistance Mechanisms in Gram-Positive Bacteria. The prevalence of resistance in Gram-positive bacterial infections is rapidly rising, presenting a pressing global challenge for both healthcare systems and economies. The WHO categorizes these bacteria into critical, high, and medium priority groups based on the urgency for developing new antibiotics. While the first priority pathogen list was issued in 2017, the 2024 list remains largely unchanged. Despite six years having passed, the progress that has been made in developing novel treatment approaches remains insufficient, allowing antimicrobial resistance to persist and worsen on a global scale. Various strategies have been implemented to address this growing threat by targeting specific resistance mechanisms. This review evaluates antimicrobial resistance (AMR) in Gram-positive bacteria, highlighting its critical impact on global health due to the rise of multidrug-resistant pathogens. It focuses on the unique cell wall structure of Gram-positive bacteria, which influences their identification and susceptibility to antibiotics. The review explores the mechanisms of AMR, including enzymatic inactivation, modification of drug targets, limiting drug uptake, and increased drug efflux. It also examines the resistance strategies employed by high-priority Gram-positive pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium, as identified in the WHO's 2024 priority list.202439766587
9800100.9999Regulation of beta-lactamase induction in gram-negative bacteria: a key to understanding the resistance puzzle. Infections caused by drug-resistant microorganisms have posed a medical challenge since the advent of antimicrobial therapy. With the emergence of resistant strains, new antibiotics were available and introduced with great success until this decade. The appearance of multiresistant microorganisms pose a real and immediate public health concern. Are we entering into the post-antibiotic era? Will we return to pre-antimicrobial-era conditions, with morbidity and mortality resulting from untreatable infectious complications? The race to stay ahead of multiresistance involves not only continued drug development and selective use but elucidation of bacterial regulation of resistance. One way to ensure continued success of antimicrobial therapy is the identification of new bacterial targets--genes and their products involved in regulating or mediating resistance. Discussion will focus on one well-defined resistance mechanism in Gram-negative bacteria, the chromosomally located amp operon, responsible for one mechanism of beta-lactam resistance.19947723996
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
9439120.9998Antimicrobial 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
9576130.9998Review 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
4329140.9998Bacterial resistance: new threats, new challenges. Bacterial resistance remains a major concern. Recently, genetic transfers from saprophytic, non-pathogenic, species to pathogenic S. pneumoniae and N. meningitidis have introduced multiple changes in the penicillin target molecules, leading to rapidly growing penicillin resistance. In enterobacteriaceae, a succession of minute mutations has generated new beta-lactamases with increasingly expanded spectrum, now covering practically all available beta-lactam antibiotics. Resistance emerges in the hospital environment but also, and increasingly, in the community bacteria. Widespread resistance is probably associated with antibiotic use, abuse and misuse but direct causality links are difficult to establish. In some countries as in some hospitals, unusual resistance profiles seem to correspond to unusual antibiotic practices. For meeting the resistance challenge, no simple solutions are available, but combined efforts may help. For improving the situation, the following methods can be proposed. At the world level, a better definition of appropriate antibiotic policies should be sought, together with strong education programmes on the use of antibiotics and the control of cross-infections, plus controls on the strategies used by pharmaceutical companies for promoting antibiotics. At various local levels, accurate guidelines should be adapted to each institution and there should be regularly updated formularies using scientific, and not only economic, criteria; molecular technologies for detecting subtle epidemic variations and emergence of new genes should be developed and regular information on the resistance profiles should be available to all physicians involved in the prevention and therapy of infections.19938149138
4243150.9998Action 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
9799160.9998Microbiology and drug resistance mechanisms of fully resistant pathogens. The acquisition of vancomycin resistance by Gram-positive bacteria and carbapenem resistance by Gram-negative bacteria has rendered some hospital-acquired pathogens impossible to treat. The resistance mechanisms employed are sophisticated and very difficult to overcome. Unless alternative treatment regimes are initiated soon, our inability to treat totally resistant bacteria will halt other developments in medicine. In the community, Gram-positive bacteria responsible for pneumonia could become totally resistant leading to increased mortality from this common infection, which would have a more immediate impact on our current lifestyles.200415451497
4064170.9998Antimicrobial 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
9804180.9998Antimicrobial 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
4318190.9998Emerging problems of antibiotic resistance in community medicine. Emergence of antimicrobial resistance in bacteria associated with community acquired infections has made the choice of empirical therapy more difficult and more expensive. The problems due to possible spread of MRSA to the community, emergence of penicillin resistance in S. pneumoniae, ampicillin resistance in H. influenzae, and multiresistance among common enteric pathogens are highlighted. Bacteria have a remarkable ability to develop resistance to many of the newly synthesized antimicrobial agents but the appropriate use of antibiotics will delay and in many cases prevent the emergence of resistance.199610879217