1990S - Word Related Documents




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249300.9640Multidrug-resistant hypervirulent Klebsiella pneumoniae: an evolving superbug. Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) combines high pathogenicity with multidrug resistance to become a new superbug. MDR-hvKP reports continue to emerge, shattering the perception that hypervirulent K. pneumoniae (hvKP) strains are antibiotic sensitive. Patients infected with MDR-hvKP strains have been reported in Asia, particularly China. Although hvKP can acquire drug resistance genes, MDR-hvKP seems to be more easily transformed from classical K. pneumoniae (cKP), which has a strong gene uptake ability. To better understand the biology of MDR-hvKP, this review discusses the virulence factors, resistance mechanisms, formation pathways, and identification of MDR-hvKP. Given their destructive and transmissible potential, continued surveillance of these organisms and enhanced control measures should be prioritized.202540135944
22310.9637Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria. Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy.202337760679
981120.9632"Infectious Supercarelessness" in Discussing Antibiotic-Resistant Bacteria. Many bacterial pathogens are exhibiting resistance to increasing numbers of antibiotics making it much more challenging to treat the infections caused by these microbes. In many reports in the media and perhaps even in discussions among physicians and biomedical scientists, these bacteria are frequently referred to as "bugs" with the prefix "super" appended. This terminology has a high potential to elicit unjustified inferences and fails to highlight the broader evolutionary context. Understanding the full range of biological and evolutionary factors that influence the spread and outcomes of infections is critical to formulating effective individual therapies and public health interventions. Therefore, more accurate terminology should be used to refer these multidrug-resistant bacteria.201628174759
251730.9631The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase-producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens.201728375512
486640.9629Resistance to polymyxins in Gram-negative organisms. Polymyxins have recently been re-introduced into the therapeutic arsenal to combat infections caused by multidrug-resistant Gram-negative bacteria. However, the emergence of strains resistant to these last-resort drugs is becoming a critical issue in a growing number of countries. Both intrinsic and transferable mechanisms of polymyxin resistance have been characterised. These mechanisms as well as the epidemiological data regarding four relevant bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) are considered in this review. A special focus is made on plasmid-mediated resistance and the spread of mcr genes.201728163137
249650.9629Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance. The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii.202032971809
488160.9627Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics. Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.201931354944
502570.9626An Update of Mobile Colistin Resistance in Non-Fermentative Gram-Negative Bacilli. Colistin, the last resort for multidrug and extensively drug-resistant bacterial infection treatment, was reintroduced after being avoided in clinical settings from the 1970s to the 1990s because of its high toxicity. Colistin is considered a crucial treatment option for Acinetobacter baumannii and Pseudomonas aeruginosa, which are listed as critical priority pathogens for new antibiotics by the World Health Organization. The resistance mechanisms of colistin are considered to be chromosomally encoded, and no horizontal transfer has been reported. Nevertheless, in November 2015, a transmissible resistance mechanism of colistin, called mobile colistin resistance (MCR), was discovered. Up to ten families with MCR and more than 100 variants of Gram-negative bacteria have been reported worldwide. Even though few have been reported from Acinetobacter spp. and Pseudomonas spp., it is important to closely monitor the epidemiology of mcr genes in these pathogens. Therefore, this review focuses on the most recent update on colistin resistance and the epidemiology of mcr genes among non-fermentative Gram-negative bacilli, especially Acinetobacter spp. and P. aeruginosa.202235782127
816480.9626Antibiotic Resistance - A Cause for Reemergence of Infections. This article can rightly be called 'the rise of the microbial phoenix'; for, all the microbial infections whose doomsday was predicted with the discovery of antibiotics, have thumbed their noses at mankind and reemerged phoenix like. The hubris generated by Sir Alexander Fleming's discovery of Penicillin in 1928, exemplified best by the comment by William H Stewart, the US Surgeon General in 1967, "It is time to close the books on infectious diseases" has been replaced by the realisation that the threat of antibiotic resistance is, in the words of the Chief Medical Officer of England, Dame Sally Davies, "just as important and deadly as climate change and international terrorism". Antimicrobial resistance threatens to negate all the major medical advances of the last century because antimicrobial use is linked to many other fields like organ transplantation and cancer chemotherapy. Antibiotic resistance genes have been there since ancient times in response to naturally occurring antibiotics. Modern medicine has only driven further evolution of antimicrobial resistance by use, misuse, overuse and abuse of antibiotics. Resistant bacteria proliferate by natural selection when their drug sensitive comrades are removed by antibiotics. In this article the authors discuss the various causes of antimicrobial resistance and dwell in some detail on antibiotic resistance in gram-positive and gram-negative organisms. Finally they stress on the important role clinicians have in limiting the development and spread of antimicrobial resistance.202032026301
978890.9625Global antibacterial resistance: The never-ending story. Bacterial resistance is undoubtedly recognised as a major medical challenge in most healthcare systems. Resistance-determining genes, mostly in combination, and multidrug-resistant (MDR) pathogens are spreading with unprecedented speed. Well known resistance carriers with high clinical impact include the Gram-positive organisms Staphylococcus aureus and Enterococcus spp. In contrast to these organisms that are usually still treatable with newer alternative antibacterial drugs, some Gram-negative bacteria, especially Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp., have developed resistance to most or all available antibiotics. Such strains are already a reality in some Mediterranean and Asian countries. According to their resistance epidemiology (based on major drivers favouring resistance), three regions are pinpointed as high-impact resistance hot spots. Despite the clear medical need for novel antibiotics without cross-resistance issues, antibacterial research and development pipelines are nearly dry, thus failing to provide the flow of novel antibiotics required to match the fast emergence and spread of MDR bacteria. In a globalised world, only concerted global actions can mitigate a future with untreatable infectious diseases.201327873580
4854100.9625Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria. Carbapenem resistance in gram-negative bacteria has caused a global epidemic that continues to grow. Although carbapenemase-producing Enterobacteriaceae have received the most attention because resistance was first reported in these pathogens in the early 1990s, there is increased awareness of the impact of carbapenem-resistant nonfermenting gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Moreover, evaluating the problem of carbapenem resistance requires the consideration of both carbapenemase-producing bacteria as well as bacteria with other carbapenem resistance mechanisms. Advances in rapid diagnostic tests to improve the detection of carbapenem resistance and the use of large, population-based datasets to capture a greater proportion of carbapenem-resistant organisms can help us gain a better understanding of this urgent threat and enable physicians to select the most appropriate antibiotics.201931724045
4850110.9624Antimicrobial Resistance in Romania: Updates on Gram-Negative ESCAPE Pathogens in the Clinical, Veterinary, and Aquatic Sectors. Multidrug-resistant Gram-negative bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacterales order are a challenging multi-sectorial and global threat, being listed by the WHO in the priority list of pathogens requiring the urgent discovery and development of therapeutic strategies. We present here an overview of the antibiotic resistance profiles and epidemiology of Gram-negative pathogens listed in the ESCAPE group circulating in Romania. The review starts with a discussion of the mechanisms and clinical significance of Gram-negative bacteria, the most frequent genetic determinants of resistance, and then summarizes and discusses the epidemiological studies reported for A. baumannii, P. aeruginosa, and Enterobacterales-resistant strains circulating in Romania, both in hospital and veterinary settings and mirrored in the aquatic environment. The Romanian landscape of Gram-negative pathogens included in the ESCAPE list reveals that all significant, clinically relevant, globally spread antibiotic resistance genes and carrying platforms are well established in different geographical areas of Romania and have already been disseminated beyond clinical settings.202337175597
4896120.9624The changing ecology of bacterial infections in children. There is continued change in the organisms involved in commonly encountered infections. Although the major organisms have changed less in pediatric than in medical or surgical infections, the advances in neonatology and the chemotherapy of leukemia have resulted in cases in which infection with once uncommon organisms is now commonplace. Perhaps more disheartening has been the increasing resistance of bacteria to antibiotics. Since resistance patterns are so much a reflection of antibiotic usage patterns in an institution, each pediatrician must be aware of the species of bacteria and the resistance patterns of the bacteria isolated in his hospital, particularly in neonatal, intensive care, and burn areas where there is the highest use of antibiotics. Close interaction of pediatrician, diagnostic microbiology laboratory, and hospital epidemiologist can provide early clues to possible bacteria involved in infection, as well as suspected antibiotic resistance patterns.19761253540
2492130.9624Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention. Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.202235979498
4878140.9622Bacteria carrying mobile colistin resistance genes and their control measures, an updated review. The plasmid encoded mobile colistin resistance (MCRs) enzyme poses a significant challenge to the clinical efficacy of colistin, which is frequently employed as a last resort antibiotic for treating infections caused by multidrug resistant bacteria. This transferase catalyzes the addition of positively charged phosphoethanolamine to lipid A of the outer membrane of gram-negative bacteria, thereby facilitating the acquired colistin resistance. This review aims to summarize and critically discuss recent advancements in the distribution and pathogenesis of mcr-positive bacteria, as well as the various control measures available for treating these infections. In addition, the ecology of mcr genes, colistin-resistance mechanism, co-existence with other antibiotic resistant genes, and their impact on clinical treatment are also analyzed to address the colistin resistance crisis. These insights provide a comprehensive perspective on MCRs and serve as a valuable reference for future therapeutic approaches to effectively combat mcr-positive bacterial infections.202439516398
2498150.9622Emerging carbapenemases: a global perspective. The celestial rise in antibiotic resistance among Gram-negative bacteria has challenged both the scientific and pharmaceutical sectors. The hallmark of this general increase is the unbridled dissemination of carbapenem resistance genes, namely KPC, OXA and metallo-β-lactamase variants. In particular, the media attention given to the NDM-1 metallo-β-lactamase has highlighted the global consequences of human behaviour on spreading antibiotic resistance.201021129630
9808160.9622Understanding Recent Developments in Colistin Resistance: Mechanisms, Clinical Implications, and Future Perspectives. Colistin resistance, driven by chromosomal mutations and the spread of plasmid-mediated MCR genes, has emerged as a critical challenge in combating multidrug-resistant Gram-negative bacteria. This resistance compromises the efficacy of colistin, leading to higher treatment failure rates, prolonged hospitalizations, and increased mortality. Recent studies have highlighted key mechanisms, including lipid A modifications, that enable bacteria to evade colistin's effects. The global spread of MCR genes exacerbates the issue, underlining the need for improved diagnostics and rapid detection of resistant strains to prevent adverse patient outcomes. To combat this growing threat, a multifaceted approach is essential, involving enhanced antimicrobial stewardship, stricter infection control measures, and continued research into alternative therapies and diagnostic methods. Collaborative efforts from researchers, healthcare providers, policymakers, and the pharmaceutical industry are crucial to preserving colistin's effectiveness and mitigating the broader impact on public health.202541148650
9789170.9621Nosocomial antibiotic resistance in multiple gram-negative species: experience at one hospital with squeezing the resistance balloon at multiple sites. Increased use of antibiotics has led to the isolation of multidrug-resistant bacteria, especially in intensive care units and long-term care facilities. Resistance in specific gram-negative bacteria, including Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, is of great concern, because a growing number of reports have documented mechanisms whereby these microorganisms have become resistant to all available antibacterial agents used in therapy. Reduction in the selection of these multidrug-resistant bacteria can be accomplished by a combination of several strategies. These include having an understanding of the genetics of both innate and acquired characteristics of bacteria; knowing resistance potentials for specific antibacterials; monitoring resistance trends in bacteria designated as problematic organisms within a particular institution on a routine basis; modifying antibiotic formularies when and where needed; creating institutional education programs; and enforcing strict infection-control practices. Strategies appropriate for primary prevention of nosocomial resistance may differ from those required for control of existing epidemic or endemic resistance.200211797177
2511180.9621Klebsiella pneumoniae with Two Carbapenemases: Where Molecular Research Stands Now. Klebsiella pneumoniae is a significant pathogen causing various infections. Since the 1990s, carbapenem-resistant Klebsiella pneumoniae (CRKP) has threatened global health. Its main resistance mechanism is producing carbapenemases like KPC, NDM, OXA, IMP and VIM, which have different prevalent isoforms and resistance features. In China, KPC is the most common carbapenemase in CRKP, followed by metallo-β-lactamase (MBL). Alarmingly, an increasing number of K. pneumoniae strains carry two or more types of enzymes, making resistance more complex. This review summarizes the major carbapenemases carried by K. pneumoniae, their global spread, and plasmids of CRKP enzyme type combinations reported in existing studies. Common combinations such as KPC + metalloenzyme, bimetallic enzyme, and metalloenzyme + OXA-48 are discussed in detail, including their genetic environments and transfer characteristics. Whole genome sequencing technology plays a crucial role in studying drug resistance genes of K. pneumoniae, facilitating in - depth identification and analysis of bacteria, and being useful for outbreak investigation and epidemiological surveillance. In conclusion, resistance genes in K. pneumoniae are often located on mobile elements. Different resistance genes tend to be carried by specific plasmids, which have high transformation rates and little impact on host growth. In order to prevent the emergence of Klebsiella pneumoniae carrying multiple drug-resistant genes, several measures such as the rational use of antibiotics, earlier monitoring of the transmission trajectory of strains, and the prediction of the development direction of drug resistance as much as possible are particularly important in the world today.202540979938
2518190.9621Plasmids Carrying Antimicrobial Resistance Genes in Gram-Negative Bacteria. Gram-negative bacteria are prevalent pathogens associated with hospital-acquired infections (HAI) that are a major challenge for patient safety, especially in intensive care units [...].202236014095