Resistance of bacteria to antibacterial agents: report of Task Force 2. - Related Documents




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423601.0000Resistance of bacteria to antibacterial agents: report of Task Force 2. The use of a growing number of antibacterial agents over the past half century has elicited a widespread deployment of genes for resistance to these agents in populations of bacteria throughout the world. Task Force 2 of the NIH Study on Antibiotic Use and Antibiotic Resistance Worldwide found that data on prevalence of resistance was fragmentary and underanalyzed but indicative of several trends. Resistance to older antibacterial agents appears to have stabilized overall, but shifts of resistance genes into new strains and species have continued to cause new clinical problems. Resistance to newer antibacterial agents has increased. Resistance is more prevalent in developing countries. Systematic surveillance of resistance integrated with understanding of its molecular basis is needed for control of resistance.19873299646
980110.9999Problems 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
423720.9999Antibiotics: action and resistance in gram-negative bacteria. Therapeutic control of beta-lactamase-producing bacteria has been a major clinical problem in the past 40 years. Gram-negative bacteria are most often resistant to antibiotics as a result of the acquisition of resistant genes or gene mutation. Studies have shown that newly developed antibiotics will shortly fail to be active against the bacteria because of the emergence of resistance. Some resistant bacteria have been found to exist even before the antibiotic was developed. Selective pressure by the antibiotic is, therefore, one of the major factors to explain the increase of resistance. Recently, numerous resistant mechanisms that differ in their substrate profiles have been described at increasing frequencies. The inappropriate use of new antibiotics with extended spectrum further complicated the problem. Because resistance is a largely unavoidable consequence of widespread use of antibiotics, it is crucial that the use of drugs is selective by exercising prudent judgment and not excessive. The actual prevalence of resistance should be continuously monitored each year. Caution should be paid to the direct extrapolation of study results from other geographic areas, because the local prevalence of resistance is unlikely to be identical to those reported elsewhere. The impact of resistance to an antibiotic and its specific mechanisms, including transmissibility, should also be carefully studied. Such information may help in designing strategies for maximizing the therapeutic usefulness of drugs and minimizing the emergence of resistance.200211950113
405830.9999Antimicrobial resistance: a complex issue. The discovery of antibiotics represented a turning point in human history. However, by the late 1950s infections that were difficult to treat, involving resistant bacteria, were being reported. Nowadays, multiresistant strains have become a major concern for public and animal health. Antimicrobial resistance is a complex issue, linked to the ability of bacteria to adapt quickly to their environment. Antibiotics, and antimicrobial-resistant bacteria and determinants, existed before the discovery and use of antibiotics by humans. Resistance to antimicrobial agents is a tool that allows bacteria to survive in the environment, and to develop. Resistance genes can be transferred between bacteria by horizontal transfer involving three mechanisms: conjugation, transduction and transformation. Resistant bacteria can emerge in any location when the appropriate conditions develop. Antibiotics represent a powerful selector for antimicrobial resistance in bacteria. Reducing the use of antimicrobial drugs is one way to control antimicrobial resistance; however, a full set of measures needs to be implemented to achieve this aim.201222849265
433340.9999New trends in regulatory rules and surveillance of antimicrobial resistance in bacteria of animal origin. Since the introduction in the 1940s of antibiotics as drugs against bacterial infections in human and then veterinary medicine, two major events have caused a shift in the antibiotherapy era: (1) the emergence of resistant bacteria and (2) the awareness of the limits of new drug development. It rapidly became urgent to set up measures in order to evaluate the importance of resistant bacteria and their origin as well as to limit the dissemination of resistant vectors (bacteria and bacterial genes). This led to the establishment of guidelines and regulatory rules necessary for risk assessment and clearly dependent upon monitoring and research organisations. At a veterinary level, the possible dissemination of multiresistant bacteria from animals to humans, through feeding, urged various national European and international institutions to give general recommendations to monitor and contain the emergence and diffusion of resistant strains. This paper gives an overview of the evolution of regulatory rules and monitoring systems dealing with multiresistant bacteria.200111432426
406150.9999Beyond 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
424560.9999Antimicrobial 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
406470.9999Antimicrobial 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
424280.9999The basis of antibiotic resistance in bacteria. The ability of bacteria to resist the inhibitory and lethal actions of antibiotics is a major clinical problem, and has been observed with every antimicrobial agent. In this article, the major mechanisms of antibiotic resistance are reviewed, and the clinical relevance of such resistance in selected bacteria is discussed.19902192071
429490.9999Anaerobic 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
9800100.9998Regulation 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
4318110.9998Emerging 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
4328120.9998Bugs 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
4331130.9998Infectious drug resistance. The emergence of antibiotic-resistant bacteria is a serious threat to public health. Infectious drug resistance, the transmission of resistant determinants from antibiotic-resistant bacteria to antibiotic-sensitive bacterial populations, creates clinical problems that must be addressed. Adequate knowledge of the mechanisms responsible for bacteria resistance is important for ensuring the benefits of antimicrobial therapy.19853981648
9438140.9998The 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
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
4059160.9998The prevention of antibiotic resistance during treatment. Prevention of emergence of antibiotic resistance during treatment is an important goal when prescribing antimicrobials. Antibiotic resistant bacteria can emerge in three main ways--by acquisition of new genes via transposons or horizontal gene transfer, by selection of resistant variants and by selection of naturally resistant strains. In order to minimize emergence of antibiotic resistance during therapy it is important to try and avoid antibiotics which encourage the transfer of resistance genes, to avoid selection of resistant variants from susceptible pathogens and to avoid ablation of antibiotic susceptible normal flora. However, implementing these objectives is not always easy. This paper discusses possible ways of limiting the emergence of resistant bacteria during treatment. It does not consider how to prevent the spread of these strains from person to person. The prevalence of antibiotic-resistant bacteria depends upon the selection of antibiotic-resistant strains and spread of these strains from person to person. Prevention therefore consists of two parts--the prevention of acquisition of resistance/selection of antibiotic-resistant variants and interrupting the mechanisms by which person-to-person spread can occur. This paper considers only the first of these two influences on prevalence of resistance.199910885824
4317170.9998Development and spread of bacterial resistance to antimicrobial agents: an overview. Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The emergence and spread of multiply resistant organisms represent the convergence of a variety of factors that include mutations in common resistance genes that extend their spectrum of activity, the exchange of genetic information among microorganisms, the evolution of selective pressures in hospitals and communities that facilitate the development and spread of resistant organisms, the proliferation and spread of multiply resistant clones of bacteria, and the inability of some laboratory testing methods to detect emerging resistance phenotypes. Twenty years ago, bacteria that were resistant to antimicrobial agents were easy to detect in the laboratory because the concentration of drug required to inhibit their growth was usually quite high and distinctly different from that of susceptible strains. Newer mechanisms of resistance, however, often result in much more subtle shifts in bacterial population distributions. Perhaps the most difficult phenotypes to detect, as shown in several proficiency testing surveys, are decreased susceptibility to beta-lactams in pneumococci and decreased susceptibility to vancomycin in staphylococci. In summary, emerging resistance has required adaptations and modifications of laboratory diagnostic techniques, empiric anti-infective therapy for such diseases as bacterial meningitis, and infection control measures in health care facilities of all kinds. Judicious use is imperative if we are to preserve our arsenal of antimicrobial agents into the next decade.200111524705
4316180.9998Why do antimicrobial agents become ineffectual? Antibiotic resistance has evolved over the past 50 years from a merely microbiological curiosity to a serious medical problem in hospitals all over the world. Resistance has been reported in almost all species of gram-positive and -negative bacteria to various classes of antibiotics including recently developed ones. Bacteria acquire resistance by reducing permeability and intracellular accumulation, by alteration of targets of antibiotic action, and by enzymatic modification of antibiotics. Inappropriate use of an antibiotic selects resistant strains much more frequently. Once resistant bacteria has emerged, the resistance can be transferred to other bacteria by various mechanisms, resulting in multiresistant strains. MRSA is one of the typical multiresistant nosocomial pathogens. A study of the PFGE pattern of endonuclease-digested chromosomal DNA showed that MRSA of a few clones were disseminated among newborns in the NICU of a Japanese hospital. In this regard, it is important to choose appropriate antibiotics and then after some time, to change to other classes to reduce the selection of resistant strains. Since the development of epoch-making new antibiotics is not expected in the near future, it has become very important to use existing antibiotics prudently based on mechanisms of antibiotic action and bacterial resistance. Control of nosocomial infection is also very important to reduce further spread of resistant bacteria.199810097676
9571190.9998Antimicrobial Resistance. Antimicrobial resistance is developing rapidly and threatens to outstrip the rate at which new antimicrobials are introduced. Genetic recombination allows bacteria to rapidly disseminate genes encoding for antimicrobial resistance within and across species. Antimicrobial use creates a selective evolutionary pressure, which leads to further resistance. Antimicrobial stewardship, best use, and infection prevention are the most effective ways to slow the spread and development of antimicrobial resistance.202032891221