The impact of different antibiotic regimens on the emergence of antimicrobial-resistant bacteria. - Related Documents




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429201.0000The 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
429510.9999Antibiotic 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
429320.9999Resistance 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
429430.9999Anaerobic 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
431740.9999Development 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
439150.9999'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
426260.9999Fitness cost of antibiotic susceptibility during bacterial infection. Advances in high-throughput DNA sequencing allow for a comprehensive analysis of bacterial genes that contribute to virulence in a specific infectious setting. Such information can yield new insights that affect decisions on how to best manage major public health issues such as the threat posed by increasing antimicrobial drug resistance. Much of the focus has been on the consequences of the selective advantage conferred on drug-resistant strains during antibiotic therapy. It is thought that the genetic and phenotypic changes that confer resistance also result in concomitant reductions in in vivo fitness, virulence, and transmission. However, experimental validation of this accepted paradigm is modest. Using a saturated transposon library of Pseudomonas aeruginosa, we identified genes across many functional categories and operons that contributed to maximal in vivo fitness during lung infections in animal models. Genes that bestowed both intrinsic and acquired antibiotic resistance provided a positive in vivo fitness advantage to P. aeruginosa during infection. We confirmed these findings in the pathogenic bacteria Acinetobacter baumannii and Vibrio cholerae using murine and rabbit infection models, respectively. Our results show that efforts to confront the worldwide increase in antibiotic resistance might be exacerbated by fitness advantages that enhance virulence in drug-resistant microbes.201526203082
980370.9999Combating antibiotic resistance in bacteria. Combinations of certain antibiotics select against resistant strains of bacteria. This finding may provide a strategy of combating antibiotic resistant bacteria.200723100665
943880.9999The 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
431890.9999Emerging 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
4329100.9999Bacterial 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
9575110.9999Antibiotic 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
4327120.9999Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Organisms causing nosocomial infection are frequently resistant to antimicrobial agents. Studies of the reasons for this have been hindered by difficulties in defining terms, by selection biases, by artifacts produced by study methods, and by failure to control for confounding variables. Major factors leading to increased prevalence of resistant organisms in hospitals are changes in organisms causing nosocomial infection (due in part to changes in characteristics of hospital populations and in procedures and instruments used in patient care), increasing prevalence of resistance in bacteria causing community-acquired infection, and use of antimicrobial agents. A causal relationship between antibiotic usage and resistance of hospital organisms is supported by consistent association and concurrent variation in several populations, presence of a dose-response pattern, and existence of a reasonable biologic model to explain the relationship. Major influences on emergence of resistant hospital bacteria include antimicrobial effects in treated individuals, mechanisms for transfer of resistance between bacteria, and routes of transmission within the hospital for bacteria or their resistance factors. Barrier isolation techniques can help control resistant hospital bacteria. However, virtually all reports agree that careful, discriminating use of antimicrobial agents remains the keystone for minimizing this problem. This need must be communicated more effectively to prescribers.19836318289
4118130.9999Antimicrobial resistance in livestock. Antimicrobial resistance may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs. Related problems are now arising in human medicine, such as the appearance of multi-resistant food-borne pathogens. Product characteristics, dose, treatment interval and duration of treatment influence the selection pressure for antimicrobial drug resistance. There are theoretical, experimental and clinical indications that the emergence of de novo resistance in a pathogenic population can be prevented by minimizing the time that suboptimal drug levels are present in the infected tissue compartment. Until recently, attention has been focused on target pathogens. However, it should be kept in mind that when antimicrobial drugs are used in an individual, resistance selection mainly affects the normal body flora. In the long term, this is at least equally important as resistance selection in the target pathogens, as the horizontal transfer of resistance genes converts almost all pathogenic bacteria into potential recipients for antimicrobial resistance. Other factors contributing to the epidemiology of antimicrobial resistance are the localization and size of the microbial population, and the age, immunity and contact intensity of the host. In livestock, dynamic herd-related resistance patterns have been observed in different animal species.200312667177
4058140.9999Antimicrobial 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
4291150.9999Reduced 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
9805160.9999Molecular 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
4061170.9999Beyond 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
4328180.9999Bugs 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
4075190.9999Antimicrobial 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