Multidrug-resistant Gram-negative bacteria: a product of globalization. - Related Documents




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501801.0000Multidrug-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
501910.9999Extended-spectrum beta-lactamases: definition, history, an update on their genetic environment and detection methods. Bacterial resistance remains a major challenge in the therapeutic field. Beta-lactam antibiotics are widely used to treat Enterobacteriaceae, especially third-generation cephalosporins (3GCs), which are used in infections caused by bacteria resistant to first- and second-line antibiotics. However, these bacteria have been able to develop resistance against the used antibiotics through the production of extended-spectrum beta-lactamase (ESBL) enzymes. These enzymes inactivate 3GCs and are sensitive to beta-lactamase inhibitors such as clavulanic acid. This resistance is acquired by plasmids (IncF, IncI, IncK…) which carry mobile genetic elements (insertion sequence, transposon…) with genes coding for these enzymes, namely, the bla (CTX-M), bla (SHV) and bla (TEM), which code for the most frequent types of ESBL (CTX-M, SHV and TEM). Unfortunately, when ESBLs are not identified in time, appropriate treatment is delayed, reducing the chances of cure. Current data highlight the spread and dangerousness of ESBL-producing bacteria worldwide and confirm the priority given to these bacteria by the World Health Organization, which insists on vigilance in identifying them, both in patients and through surveillance studies. The aim of the current review is to provide a better understanding of ESBLs, to highlight their historical evolution and to show the importance of their genetic environment in the dissemination and spread of these enzymes worldwide, as well as the techniques used to detect them in laboratory studies. Current data demonstrate the degree of danger posed by ESBL-producing bacteria and confirm the priority given to these bacteria by the World Health Organization for the development of new antimicrobial agents.202540554694
251720.9999The 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
486330.9999Carbapenem Resistance in Gram-Negative Bacteria: The Not-So-Little Problem in the Little Red Dot. Singapore is an international travel and medical hub and faces a genuine threat for import and dissemination of bacteria with broad-spectrum resistance. In this review, we described the current landscape and management of carbapenem resistance in Gram-negative bacteria (GNB) in Singapore. Notably, the number of carbapenem-resistant Enterobacteriaceae has exponentially increased in the past two years. Resistance is largely mediated by a variety of mechanisms. Polymyxin resistance has also emerged. Interestingly, two Escherichia coli isolates with plasmid-mediated mcr-1 genes have been detected. Evidently, surveillance and infection control becomes critical in the local setting where resistance is commonly related to plasmid-mediated mechanisms, such as carbapenemases. Combination antibiotic therapy has been proposed as a last-resort strategy in the treatment of extensively drug-resistant (XDR) GNB infections, and is widely adopted in Singapore. The diversity of carbapenemases encountered, however, presents complexities in both carbapenemase detection and the selection of optimal antibiotic combinations. One unique strategy introduced in Singapore is a prospective in vitro combination testing service, which aids physicians in the selection of individualized combinations. The outcome of this treatment strategy has been promising. Unlike countries with a predominant carbapenemase type, Singapore has to adopt management strategies which accounts for diversity in resistance mechanisms.201627681907
502840.9999The 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
502750.9999Vegetables and Fruit as a Reservoir of β-Lactam and Colistin-Resistant Gram-Negative Bacteria: A Review. Antibacterial resistance is one of the 2019 World Health Organization's top ten threats to public health worldwide. Hence, the emergence of β-lactam and colistin resistance among Gram-negative bacteria has become a serious concern. The reservoirs for such bacteria are increasing not only in hospital settings but in several other sources, including vegetables and fruit. In recent years, fresh produce gained important attention due to its consumption in healthy diets combined with a low energy density. However, since fresh produce is often consumed raw, it may also be a source of foodborne disease and a reservoir for antibiotic resistant Gram-negative bacteria including those producing extended-spectrum β-lactamase, cephalosporinase and carbapenemase enzymes, as well as those harboring the plasmid-mediated colistin resistance (mcr) gene. This review aims to provide an overview of the currently available scientific literature on the presence of extended-spectrum β-lactamases, cephalosporinase, carbapenemase and mcr genes in Gram-negative bacteria in vegetables and fruit with a focus on the possible contamination pathways in fresh produce.202134946136
485560.9999Carbapenem-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
502170.9999Beta-lactamases in Enterobacteriaceae infections in children. Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.201627180312
154780.9999The 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
484490.9999Genetic basis of molecular mechanisms in β-lactam resistant gram-negative bacteria. Antibiotic-resistant bacteria are considered one of the major global threats to human and animal health. The most harmful among the resistant bacteria are β-lactamase producing Gram-negative species (β-lactamases). β-lactamases constitute a paradigm shift in the evolution of antibiotic resistance. Therefore, it is imperative to present a comprehensive review of the mechanisms responsible for developing antimicrobial resistance. Resistance due to β-lactamases develops through a variety of mechanisms, and the number of resistant genes are involved that can be transferred between bacteria, mostly via plasmids. Over time, these new molecular-based resistance mechanisms have been progressively disclosed. The present review article provides information on the recent findings regarding the molecular mechanisms of resistance to β-lactams in Gram-negative bacteria, including CTX-M-type ESBLs with methylase activity, plasmids harbouring phages with β-lactam resistance genes, the co-presence of β-lactam resistant genes of unique combinations and the presence of β-lactam and non-β-lactam antibiotic-resistant genes in the same bacteria. Keeping in view, the molecular level resistance development, multifactorial and coordinated measures may be taken to counter the challenge of rapidly increasing β-lactam resistance.202134119627
2513100.9999Prevalence 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
2514110.9999Characteristics 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
5020120.9999Detection of expanded-spectrum β-lactamases in Gram-negative bacteria in the 21st century. Emerging β-lactamase-producing-bacteria (ESBL, AmpC and carbapenemases) have become a serious problem in our community due to their startling spread worldwide and their ability to cause infections which are difficult to treat. Diagnosis of these β-lactamases is of clinical and epidemiological interest. Over the past 10 years, several methods have been developed aiming to rapidly detect these emerging enzymes, thus preventing their rapid spread. In this review, we describe the range of screening and detection methods (phenotypic, molecular and other) for detecting these β-lactamases but also whole genome sequencing as a tool for detecting the genes encoding these enzymes.201526162631
4862130.9999Genetic 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
5017140.9998Evolution of β-lactams resistance in Gram-negative bacteria in Tunisia. Antimicrobial resistance is a major health problem worldwide, but marked variations in the resistance profiles of bacterial pathogens are found between countries and in different patient settings. In Tunisia, the strikingly high prevalence of resistance of bacteria to penicillins and cephalorosporins drugs including fourth generation in clinical isolates of Gram negative bacteria has been reported. During 30 years, the emerging problem of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates is substantial, and some unique enzymes have been found. Recently, evidence that Gram-negative bacteria are resistant to nearly all available antimicrobial agents, including carbapenems, have emerged.201121438848
5030150.9998Characterization of ESBL disseminating plasmids. Bacteria producing extended-spectrum β-lactamases (ESBLs) constitute a globally increasing problem that contributes to treatment complications and elevated death rates. The extremely successful dissemination by ESBL-producing Enterobacteriaceae during the latest decades is a result of the combination of mobilization, evolution and horizontal spread of β-lactamase genes on plasmids. In parallel, spread of these plasmids to particularly well-adapted bacterial clones (outbreak clones) has expanded. In this review we describe ESBL-producing bacteria and the genetic mechanisms for dissemination of ESBL resistance. We describe available methodology for studying plasmids and the importance of including plasmids in epidemiological typing as natural parts of the organisms. Plasmids play a fundamental role in how resistance arises and disseminates.201626135711
4867160.9998Metallo Beta Lactamase Enzymes. Multidrug resistance has become more common in Gram-negative bacteria, making them one of the emerging public health problems with extremely detrimental effects on the world economy. These drugs are broad-spectrum-lactam antibiotics used as a last-resort treatment against multidrug-resistant microorganisms (MDROs). As the resistance to these last-line drugs grows, so does the need to detect and deal with MDROs that carbapenem-resistant. The group B carbapenemases, such as Imipenem metallo-lactamases (IMP) and Verona integron-encoded metallo-lactamases (VIM), are the most prevalent. Integrons, which also include various antibiotic resistance genes, contain the genes for IMP and VIM, promoting their worldwide proliferation. Many papers reported that spreading genes of these enzymes among bacteria rapidly nowadays had had a negative effect on infection control. This review can help with ensuring the understanding of carbapenem resistance as well as policies for eradications and declination of resistance mechanisms that are critical not only for therapeutic treatment but also for infection control measures and epidemic investigations and detections. This review aims to comprehend the mechanism of resistance and transmission of these elements.202540655350
5016170.9998Broad-spectrum β-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health. Broad-spectrum β-lactamase genes (coding for extended-spectrum β-lactamases and AmpC β-lactamases) have been frequently demonstrated in the microbiota of food-producing animals. This may pose a human health hazard as these genes may be present in zoonotic bacteria, which would cause a direct problem. They can also be present in commensals, which may act as a reservoir of resistance genes for pathogens causing disease both in humans and in animals. Broad-spectrum β-lactamase genes are frequently located on mobile genetic elements, such as plasmids, transposons and integrons, which often also carry additional resistance genes. This could limit treatment options for infections caused by broad-spectrum β-lactam-resistant microorganisms. This review addresses the growing burden of broad-spectrum β-lactam resistance among Enterobacteriaceae isolated from food, companion and wild animals worldwide. To explore the human health hazard, the diversity of broad-spectrum β-lactamases among Enterobacteriaceae derived from animals is compared with respect to their presence in human bacteria. Furthermore, the possibilities of the exchange of genes encoding broad-spectrum β-lactamases - including the exchange of the transposons and plasmids that serve as vehicles for these genes - between different ecosystems (human and animal) are discussed.201020030731
4851180.9998A 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
4861190.9998The Challenge of Global Emergence of Novel Colistin-Resistant Escherichia coli ST131. Escherichia coli ST131 is one of the high-risk multidrug-resistant clones with a global distribution and the ability to persist and colonize in a variety of niches. Carbapenemase-producing E. coli ST131 strains with the ability to resist last-line antibiotics (i.e., colistin) have been recently considered a significant public health. Colistin is widely used in veterinary medicine and therefore, colistin-resistant bacteria can be transmitted from livestock to humans through food. There are several mechanisms of resistance to colistin, which include chromosomal mutations and plasmid-transmitted mcr genes. E. coli ST131 is a great model organism to investigate the emergence of superbugs. This microorganism has the ability to cause intestinal and extraintestinal infections, and its accurate identification as well as its antibiotic resistance patterns are vitally important for a successful treatment strategy. Therefore, further studies are required to understand the evolution of this resistant organism for drug design, controlling the evolution of other nascent emerging pathogens, and developing antibiotic stewardship programs. In this review, we will discuss the importance of E. coli ST131, the mechanisms of resistance to colistin as the last-resort antibiotic against resistant Gram-negative bacteria, reports from different regions regarding E. coli ST131 resistance to colistin, and the most recent therapeutic approaches against colistin-resistance bacteria.202133913748