Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria. - Related Documents




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979801.0000Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria. Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.201931470632
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
431820.9999Emerging 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
979930.9999Microbiology 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
979140.9999Beta-lactam resistance and the effectiveness of antimicrobial peptides against KPC-producing bacteria. Bacterial resistance is a problem that is giving serious cause for concern because bacterial strains such as Acinetobacter baumannii and Pseudomonas aeruginosa are difficult to treat and highly opportunistic. These bacteria easily acquire resistance genes even from other species, which confers greater persistence and tolerance towards conventional antibiotics. These bacteria have the highest death rate in hospitalized intensive care patients, so strong measures must be taken. In this review, we focus on the use of antimicrobial peptides (AMPs) as an alternative to traditional drugs, due to their rapid action and lower risk of generating resistance by microorganisms. We also present an overview of beta-lactams and explicitly explain the activity of AMPs against carbapenemase-producing bacteria as potential alternative agents for infection control.202236042694
980150.9999Problems 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
432860.9999Bugs 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
431670.9999Why 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
980080.9999Regulation 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
431790.9999Development 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
9802100.9999Transient comparison of techniques to counter multi-drug resistant bacteria: prime modules in curation of bacterial infections. Multidrug-resistant organisms are bacteria that are no longer controlled or killed by specific drugs. One of two methods causes bacteria multidrug resistance (MDR); first, these bacteria may disguise multiple cell genes coding for drug resistance to a single treatment on resistance (R) plasmids. Second, increased expression of genes coding for multidrug efflux pumps, which extrude many drugs, can cause MDR. Antibiotic resistance is a big issue since some bacteria may withstand almost all antibiotics. These bacteria can cause serious sickness, making them a public health threat. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Multidrug resistant Mycobacterium tuberculosis (TB), and CRE are gut bacteria that resist antibiotics. Antimicrobial resistance is rising worldwide, increasing clinical and community morbidity and mortality. Superbugs have made antibiotic resistance in some environmental niches even harder to control. This study introduces new medicinal plants, gene-editing methods, nanomaterials, and bacterial vaccines that will fight MDR bacteria in the future.202339816650
4898110.9999Antibiotics and bacterial resistance. A few elements of genetic basis for this relationship. In the preantibiotic era, many people died of bacterial infections caused by such pathogens as Staphylococcus aureus and Streptococcus pyogenes, Streptococcus pneumoniae and Mycobacterium tuberculosis. Antibiotics have reduced the mortality from infectious diseases but not the prevalence of these diseases. It was not long after the clinical introduction of the first antibiotics in the 1950s that the first reports of bacterial resistance began to appear. Use, and often abuse or misuse, of antimicrobial agents has encouraged the evolution of bacteria toward resistance, resulting often in therapeutic failure. In the beginning, new antibiotics have always appeared in plenty of time to provide new cures for diseases caused by resistant bacterial pathogens. Also, some clinically important groups of bacteria showed no signs of major increases in resistance. For example, S. pneumoniae strains remained susceptible to penicillin long after other bacteria had become resistant to it. Recent developments of bacteria resistance to antibiotics are indeed disquieting.19958993117
4797120.9998Antibiotic resistance among clinically important gram-positive bacteria in the UK. The resistance of bacteria to antibiotics, particularly those used for first-line therapy, is an increasing cause for concern. In the UK, the prevalence of resistance to methicillin and mupirocin in Staphylococcus aureus, and to penicillin and macrolides in Streptococcus pneumoniae, appear to be increasing. There has also been an increase in the number of hospitals where glycopeptide-resistant enterococci are known to have been isolated. The increases in methicillin-resistant S. aureus and glycopeptide-resistant enterococci are due, in part, to the inter-hospital spread of epidemic strains. Although new quinolones and streptogramins with activity against Gram-positive bacteria (including strains resistant to currently available agents) are under development, there is no reason to believe that resistance to these agents will not emerge. The control of resistance in Gram-positive bacteria will require a multi-faceted approach, including continued and improved surveillance, a reduction in the unnecessary use of antibiotics, and the application of other strategies such as vaccination.19989777517
4796130.9998The specter of glycopeptide resistance: current trends and future considerations. Two glycopeptide antibiotics, vancomycin and teicoplanin, are currently available for clinical use in various parts of the world, whereas a third, avoparcin, is available for use in agricultural applications and in veterinary medicine in some countries. Because of their outstanding activity against a broad spectrum of gram-positive bacteria, vancomycin and teicoplanin have often been considered the drugs of "last resort" for serious infections due to drug-resistant gram-positive pathogens. Glycopeptides had been in clinical use for almost 30 years before high-level resistance, first reported in enterococcal species, emerged. More recently, there have been disturbing reports of low- and intermediate-level resistance to vancomycin in strains of Staphylococcus aureus. A review of earlier reports reveals, however, that S. aureus strains with reduced susceptibility to glycopeptides were first identified >40 years ago. Such strains may occur in nature or may have developed low-level mutational resistance in response to the selection pressure of glycopeptide therapy. Of considerably greater concern is the possibility that vancomycin resistance genes found in enterococci may be transferred to more virulent organisms such as staphylococci or Streptococcus pneumoniae.19989684651
4247140.9998Drug resistance in tuberculosis. Drug-resistant tuberculosis remains a worldwide problem. New laboratory methods have improved our ability to more rapidly identify resistant strains, but the most effective approach is to prevent the appearance of resistance by appropriate choice of antibiotics and directly-observed therapy. Mycobacterium tuberculosis is treated with familiar and unique drugs; consequently, mechanisms of resistance have some unique features. All drug resistance thus far identified develops by mutational events rather than acquisition of resistance genes from other bacteria. An agenda is presented for countering the appearance of further drug resistance in mycobacteria.19979421707
4897150.9998Rapid diagnosis of tuberculosis. Detection of drug resistance mechanisms. Tuberculosis is still a serious public health problem, with 10.8 million new cases and 1.8 million deaths worldwide in 2015. The diversity among members of the Mycobacterium tuberculosis complex, the causal agent of tuberculosis, is conducive to the design of different methods for rapid diagnosis. Mutations in the genes involved in resistance mechanisms enable the bacteria to elude the treatment. We have reviewed the methods for the rapid diagnosis of M. tuberculosis complex and the detection of susceptibility to drugs, both of which are necessary to prevent the onset of new resistance and to establish early, appropriate treatment.201728318570
9805160.9998Molecular 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
4895170.9998Drug resistance in leprosy: An update following 70years of chemotherapy. Leprosy is one of the oldest infectious diseases, reported for more than 2000years. Leprosy elimination goal as a public health problem set by the World Health Organization, aiming for a global prevalence rate<1 patient in a population of 10,000, was achieved in 2000 mainly thanks to the worldwide use of leprosy drugs starting in the 1980s and their access at no cost for patients since 1995. However, around 200,000 new cases are still reported each year, particularly in India, Brazil, and Indonesia. As with other bacteria of medical interest, antimicrobial resistance is observed in Mycobacterium leprae strains in several parts of the world, despite multidrug therapy being the recommended standard leprosy treatment to avoid resistance selection since 1982. Therefore, identifying and monitoring resistance is necessary. We provide an overview of the historical facts that led to the current drug resistance situation, the antibiotics effective against M. leprae, their mechanisms of action and resistance, and resistance detection methods. We also discuss therapeutic management of the resistant cases, new genes with potential roles in drug resistance and bacterial adaptation, new drugs under investigation, and the risk for resistance selection with the chemoprophylaxis measures.202235483633
4795180.9998Epidemiology and mechanisms of glycopeptide resistance in enterococci. PURPOSE OF REVIEW: This review updates epidemiologic trends and our understanding of glycopeptide resistance in enterococci. RECENT FINDINGS: Colonization and infection rates with vancomycin resistant enterococci continue to increase throughout the world while factors contributing to this rise continue to be defined. While no interventions exist to eradicate colonization, infection control procedures are cost effective and decrease the prevalence of vancomycin resistant enterococcal colonization and infection. New molecular methods show great promise in strengthening our ability to detect colonization with these bacteria. Furthermore, our understanding of the origin of vancomycin resistant enterococci continues to grow. Paenibacillus species found in soil have been found to carry homologues of vanA-associated glycopeptide resistance genes found in enterococci. Also, additional evidence supports previous data that VanB-associated resistance may have been horizontally transferred from gastrointestinal tract bacteria to enterococci. Finally, glycopeptide resistance has been transferred to methicillin-resistant Staphylococcus aureus in clinical practice on several occasions. SUMMARY: The prevalence of vancomycin resistant enterococci will likely continue to increase. Implementation of infection control strategies, in conjunction with deployment of advanced technologies for detection of vancomycin resistant enterococci, may curb this rise. The emergence of vancomycin resistant S. aureus is of concern.200516258324
4237190.9998Antibiotics: 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