Antimicrobial resistance in Klebsiella pneumoniae: an overview of common mechanisms and a current Canadian perspective. - Related Documents




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252001.0000Antimicrobial resistance in Klebsiella pneumoniae: an overview of common mechanisms and a current Canadian perspective. Klebsiella pneumoniae is a ubiquitous opportunistic pathogen of the family Enterobacteriaceae. K. pneumoniae is a member of the ESKAPEE pathogens (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli), a group of bacteria that cause nosocomial infections and are able to resist killing by commonly relied upon antimicrobial agents. The acquisition of antimicrobial resistance (AMR) genes is increasing among community and clinical isolates of K. pneumoniae, making K. pneumoniae a rising threat to human health. In addition to the increase in AMR, K. pneumoniae is also thought to disseminate AMR genes to other bacterial species. In this review, the known mechanisms of K. pneumoniae AMR will be described and the current state of AMR K. pneumoniae within Canada will be discussed, including the impact of the coronavirus disease-2019 pandemic, current perspectives, and outlook for the future.202439213659
251410.9999Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae. Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen that can cause a range of infections in hospitalized patients. With the growing use of antibiotics, MDR K. pneumoniae is more prevalent, posing additional difficulties and obstacles in clinical therapy. To provide a valuable reference to deeply understand K. pneumoniae, and also to provide the theoretical basis for clinical prevention of such bacteria infections, the antibiotic resistance and mechanism of K. pneumoniae are discussed in this article. We conducted a literature review on antibiotic resistance of K. pneumoniae. We ran a thorough literature search of PubMed, Web of Science, and Scopus, among other databases. We also thoroughly searched the literature listed in the papers. We searched all antibiotic resistance mechanisms and genes of seven important antibiotics used to treat K. pneumoniae infections. Antibiotics such as β-lactams, aminoglycosides, and quinolones are used in the treatment of K. pneumoniae infection. With both chromosomal and plasmid-encoded ARGs, this pathogen has diverse resistance genes. Carbapenem resistance genes, enlarged-spectrum β-lactamase genes, and AmpC genes are the most often β-lactamase resistance genes. K. pneumoniae is a major contributor to antibiotic resistance worldwide. Understanding K. pneumoniae antibiotic resistance mechanisms and molecular characteristics will be important for the design of targeted prevention and novel control strategies against this pathogen.202337197355
251320.9998Prevalence and molecular epidemiology of carbapenem-resistant Gram-negative bacilli and their resistance determinants in the Eastern Mediterranean Region over the last decade. Carbapenem resistance in Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa is increasing worldwide, which has led the World Health Organization (WHO) to list these bacteria in the critical priority pathogens group. Infections by such pathogens pose a serious threat to hospitalised patients and are associated with clinical and economic consequences. What worsens the case is the weak pipeline of available antimicrobial agents to treat such infections and the absence of new drugs. The aim of this review was to shed light on all studies tackling carbapenem resistance in Enterobacteriaceae, A. baumannii and P. aeruginosa in the Eastern Mediterranean region, with indication for each country, description of studies timeline, prevalence of carbapenem resistance, and carbapenem resistance-encoding genes detected in these countries.202133812049
251130.9998Klebsiella 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
485940.9998Nosocomial infection and its molecular mechanisms of antibiotic resistance. Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.201626877142
251550.9998High-risk Pseudomonas aeruginosa clones harboring β-lactamases: 2024 update. Carbapenem-resistant Pseudomonas aeruginosa is defined by the World Health Organization as a "high priority" in developing new antimicrobials. Indeed, the emergence and spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria increase the morbidity and mortality risk of infected patients. Genomic variants of P. aeruginosa that display phenotypes of MDR/XDR have been defined as high-risk global clones. In this mini-review, we describe some international high-risk clones that carry β-lactamase genes that can produce chronic colonization and increase infected patients' morbidity and mortality rates.202539850428
485560.9998Carbapenem-resistant enterobacteriaceae: an emerging problem in children. Antibiotic resistance among gram-negative bacteria has reached critical levels. The rise of carbapenem resistance in Enterobacteriaceae carrying additional resistance genes to multiple antibiotic classes has created a generation of organisms nearly resistant to all available therapy. Carbapenem-resistant Enterobacteriaceae (CRE) infections are known to be associated with significant morbidity and mortality, and these pathogens have now made their way to the most vulnerable populations, including children. This review provides a brief overview of CRE, with a focus on CRE infections in children, and highlights available data on the epidemiology, clinical characteristics, carbapenemase types, risk factors, treatment, and outcomes of these multi-drug resistant infections in the pediatric population.201222700827
251970.9998Clinical Perspective of Antimicrobial Resistance in Bacteria. Antimicrobial resistance (AMR) has become a global clinical problem in recent years. With the discovery of antibiotics, infections were not a deadly problem for clinicians as they used to be. However, worldwide AMR comes with the overuse/misuse of antibiotics and the spread of resistance is deteriorated by a multitude of mobile genetic elements and relevant resistant genes. This review provides an overview of the current situation, mechanism, epidemiology, detection methods and clinical treatment for antimicrobial resistant genes in clinical important bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), extended-spectrum β-lactamase-producing Enterobacteriaceae, acquired AmpC β-lactamase-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae (CPE), multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa.202235264857
251780.9998The 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
502890.9998The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria. Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups.202032316342
4854100.9998Epidemiology 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
4852110.9998Recent trends in antibiotic resistance in European ICUs. PURPOSE OF REVIEW: Antimicrobial resistance is an emerging problem in ICUs worldwide. As numbers of published results from national/international surveillance studies rise rapidly, the amount of new information may be overwhelming. Therefore, we reviewed recent trends in antibiotic resistance in ICUs across Europe in the past 18 months. RECENT FINDINGS: In this period, infections caused by methicillin-resistant Staphylococcus aureus appeared to stabilize (and even decrease) in some countries, and infection rates due to Gram-positive bacteria resistant to vancomycin, linezolid or daptomycin have remained low. In contrast, we are witnessing a continent-wide emergence of infections caused by multiresistant Gram-negative bacteria, especially Escherichia coli and Klebsiella pneumoniae, with easily exchangeable resistance genes located on plasmids, producing enzymes such as extended spectrum β-lactamases and carbapenamases. In the absence of new antibiotics, prevention of infections, reducing unnecessary antibiotic use, optimizing adherence to universal hygienic and infection control measures, and improving implementation of diagnostic tests are our only tools to combat this threat. SUMMARY: As the epidemiology of antibiotic resistance in ICUs is rapidly changing toward more frequently occurring epidemics and endemicity of multi and panresistant Gram-negative pathogens, better infection control and improved diagnostics will become even more important than before.201121986462
4851120.9998A global view on carbapenem-resistant Acinetobacter baumannii. Carbapenem-resistant Acinetobacter baumannii are of increasing public health importance, as they are resistant to last-line antibiotics. International clones with well-characterized resistance genes dominate globally; however, locally, other lineages with different properties may be of importance to consider. This study investigated isolates from a broad geographic origin from 114 hospitals in 47 countries and from five world regions ensuring the greatest possible diversity in an organism known for its propensity for clonal epidemic spread and reflecting the current global epidemiology of carbapenem-resistant A. baumannii. In Latin America, a lineage different from other geographic regions circulates, with a different resistance gene profile. This knowledge is important to adjust local infection prevention measures. In a global world with migration and increasing use of antimicrobials, multidrug-resistant bacteria will continue to adapt and challenge our healthcare systems worldwide.202337882512
2512130.9998Understanding and addressing β-lactam resistance mechanisms in gram-negative bacteria in Lebanon: A scoping review. BACKGROUND: A growing threat to public health is the worldwide problem of antimicrobial resistance (AMR), in which gram-negative organisms are playing a significant role. Antibiotic abuse and misuse, together with inadequate monitoring and control protocols, have contributed to the emergence of resistant strains. This global scenario prepares us to look more closely at the situation in Lebanon. The aim of this review is to investigate in detail the resistance mechanisms and related genes that are displayed by gram-negative organisms in Lebanon. METHODS: A comprehensive analysis was carried out to pinpoint and gather information regarding gram-negative bacteria displaying resistance to antibiotics. To contribute to a complete understanding of the current state of antibiotic resistance in gram-negative strains, it was intended to collect and evaluate data on these organisms' resistance patterns in a comprehensive manner. RESULTS: Several studies have emphasized the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in Lebanon, specifically noting Escherichia coli and Klebsiella pneumoniae as the most frequent culprits, with OXA-48 and NDM-1 being the primary carbapenemases discovered. Furthermore, the TEM β-lactamase families are the primary source of extended-spectrum β-lactamases (ESBLs) in Shigella and Salmonella. Additionally, resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa have been linked to nosocomial infections in the country. CONCLUSION: There is a considerable frequency of antibiotic overuse and misuse in Lebanon, based to the limited data available on antibiotic consumption. In conclusion, antibiotic stewardship initiatives and additional research beyond the confines of single-center studies in Lebanon are needed.202539981361
1547140.9997The KPC type beta-lactamases: new enzymes that confer resistance to carbapenems in Gram-negative bacilli. Antimicrobial resistance due to the continuous selective pressure from widespread use of antimicrobials in humans, animals and agriculture has been a growing problem for last decades. KPC beta-lactamases hydrolyzed beta-lactams of all classes. Especially, carbapenem antibiotics are hydrolyzed more efficiency than other beta-lactam antibiotics. The KPC enzymes are found most often in Enterobacteriaceae. Recently, these enzymes have been found in isolates of Pseudomonas aeruginosa and Acinetobacter spp. The observations of blaKPC genes isolated from different species in other countries indicate that these genes from common but unknown ancestor may have been mobilized in these areas or that blaKPC-carrying bacteria may have been passively by many vectors. The emergence of carbapenem resistance in Gram-negative bacteria is worrisome because the carbapenem resistance often may be associated with resistance to many beta-lactam and non-beta-lactam antibiotics. Treatment of infections caused by KPC-producing bacteria is extremely difficult because of their multidrug resistance, which results in high mortality rates. Therapeutic options to treat infections caused by multiresistant Gram-negative bacteria producing KPC-carbapenemases could be used polymyxin B or tigecycline.200920430717
4862150.9997Genetic Factors That Contribute to Antibiotic Resistance through Intrinsic and Acquired Bacterial Genes in Urinary Tract Infections. The overprescribing and misuse of antibiotics have led to the rapid development of multidrug-resistant bacteria, such as those that cause UTIs. UTIs are the most common outpatient infections and are mainly caused by Escherichia coli and Klebsiella spp., although some Gram-positive bacteria, such as Pseudomonas aeruginosa, have been isolated in many cases. The rise of antimicrobial-resistant bacteria is a major public health concern, as it is predicted to lead to increased healthcare costs and poor patient outcomes and is expected to be the leading cause of global mortality by 2050. Antibiotic resistance among bacterial species can arise from a myriad of factors, including intrinsic and acquired resistance mechanisms, as well as mobile genetic elements, such as transposons, integrons, and plasmids. Plasmid-mediated resistance is of major concern as drug-resistance genes can quickly and efficiently spread across bacterial species via horizontal gene transfer. The emergence of extended-spectrum β-lactamases (ESBLs) such as NDM-1, OXA, KPC, and CTX-M family members has conferred resistance to many commonly used antibiotics in the treatment of UTIs, including penicillins, carbapenems, cephalosporins, and sulfamethoxazole. This review will focus on plasmid-mediated bacterial genes, especially those that encode ESBLs, and how they contribute to antibiotic resistance. Early clinical detection of these genes in patient samples will provide better treatment options and reduce the threat of antibiotic resistance.202337374909
4865160.9997Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.201931190901
5018170.9997Multidrug-resistant Gram-negative bacteria: a product of globalization. Global trade and mobility of people has increased rapidly over the last 20 years. This has had profound consequences for the evolution and the movement of antibiotic resistance genes. There is increasing exposure of populations all around the world to resistant bacteria arising in the emerging economies. Arguably the most important development of the last two decades in the field of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group. A consequence of the very high rates of ESBL production among Enterobacteriaceae in Asian countries is that there is a substantial use of carbapenem antibiotics, resulting in the emergence of plasmid-mediated resistance to carbapenems. This article reviews the emergence and spread of multidrug-resistant Gram-negative bacteria, focuses on three particular carbapenemases--imipenem carbapenemases, Klebsiella pneumoniae carbapenemase, and New Delhi metallo-β-lactamase--and highlights the importance of control of antibiotic use.201525737092
5025180.9997An 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
1556190.9997Resistance to Colistin in Klebsiella Pneumoniae: A 4.0 Strain? The global rise of multidrug-resistant gram-negative bacteria represents an increasing threat to patient safety. From the first observation of a carbapenem-resistant gram-negative bacteria a global spread of extended-spectrum beta-lactamases and carbapenemases producing Klebsiella pneumoniae has been observed. Treatment options for multidrug-resistant K. pneumoniae are actually limited to combination therapy with some aminoglycosides, tigecycline and to older antimicrobial agents. Unfortunately, the prevalence of colistin-resistant and tigecycline-resistant K. pneumoniae is increasing globally. Infection due to colistin-resistant K. pneumoniae represents an independent risk factor for mortality. Resistance to colistin in K. pneumoniae may be multifactorial, as it is mediated by chromosomal genes or plasmids. The emergence of transmissible, plasmid-mediated colistin resistance is an alarming finding. The absence of new agents effective against resistant Gram-negative pathogens means that enhanced surveillance, compliance with infection prevention procedures, and antimicrobial stewardship programs will be required to limit the spread of colistin-resistant K. pneumoniae.201728626539