The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria. - Related Documents




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502801.0000The 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
486210.9999Genetic 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
484420.9999Genetic 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
502730.9999Vegetables 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
486340.9999Carbapenem 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
485150.9999A 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
501860.9999Multidrug-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
486870.9999Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria. Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.201322667455
485580.9999Carbapenem-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
485490.9999Epidemiology 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
5025100.9999An 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
2513110.9999Prevalence 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
5026120.9999Molecular mechanisms and clonal lineages of colistin-resistant bacteria across the African continent: a scoping review. Colistin (also known as polymyxin E), a polymyxin antibiotic discovered in the late 1940s, has recently reemerged as a last-line treatment option for multidrug-resistant infections. However, in recent years, colistin-resistant pathogenic bacteria have been increasingly reported worldwide. Accordingly, the presented review was undertaken to identify, integrate and synthesize current information regarding the detection and transmission of colistin-resistant bacteria across the African continent, in addition to elucidating their molecular mechanisms of resistance. PubMed, Google Scholar and Science Direct were employed for study identification, screening and extraction. Overall, based on the developed literature review protocol and associated inclusion/exclusion criteria, 80 studies published between 2000 and 2021 were included comprising varying bacterial species and hosts. Numerous mechanisms of colistin resistance were reported, including chromosomal mutation(s) and transferable plasmid-mediated colistin resistance (encoded by mcr genes). Perhaps unexpectedly, mcr-variants have exhibited rapid emergence and spread across most African regions. The genetic variant mcr-1 is predominant in humans, animals and the natural environment, and is primarily carried by IncHI2- type plasmid. The highest number of studies reporting the dissemination of colistin-resistant Gram-negative bacteria were conducted in the North African region.202236000241
4850130.9999Antimicrobial 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
4845140.9999The changing epidemiology of resistance. Antibiotic resistance is now a linked global problem. Dispersion of successful clones of multidrug resistant (MDR) bacteria is common, often via the movement of people. Local evolution of MDR bacteria is also important under the pressure of excessive antibiotic use, with horizontal gene transfer providing the means by which genes such as bla(CTX-M) spread amongst different bacterial species and strains. Beta-lactamase production is a common resistance mechanism in Gram-negative bacteria, and the rapid dissemination of novel genes reflects their evolution under the selective pressure of antibiotic usage. Many Enterobacteriaceae now carry broad-spectrum beta-lactamases such as CTX-M, with particular genotypes associated with different geographical regions. The spread of these enzymes has compromised the clinical utility of a number of beta-lactam classes and with the spread of genes such as bla(KPC), carbapenems may be increasingly compromised in the future. High-level fluoroquinolone resistance (mainly caused by gyrA mutations) has also been shown to be associated with CTX-M and CMY-type enzymes, commonly due to co-carriage on conjugative plasmids of the gene for the aminoglycoside-inactivating enzyme AAC-6(1)-Ib-cr and qnr genes (which confer low-level resistance), allowing the easy selection of gyrA mutants in the host strain. Resistance in Gram-positive bacteria is also widely distributed and increasing, with the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) blurring the distinction between hospital and community strains. Antibiotic use and environmental factors all have a role in the emergence and spread of resistance. This article reviews some of the new mechanisms and recent trends in the global spread of MDR bacteria.200919675017
4867150.9999Metallo 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
4877160.9999Carbapenemase-producing Gram-negative bacteria in aquatic environments: a review. Antibiotic resistance is one of the greatest public-health challenges worldwide, especially with regard to Gram-negative bacteria (GNB). Carbapenems are the β-lactam antibiotics of choice with the broadest spectrum of activity and, in many cases, are the last-resort treatment for several bacterial infections. Carbapenemase-encoding genes, mainly carried by mobile genetic elements, are the main mechanism of resistance against carbapenems in GNB. These enzymes exhibit a versatile hydrolytic capacity and confer resistance to most β-lactam antibiotics. After being considered a clinical issue, increasing attention is being giving to the dissemination of such resistance mechanisms in the environment and especially through water. Aquatic environments are among the most significant microbial habitats on our planet, known as a favourable medium for antibiotic gene transfer, and they play a crucial role in the huge spread of drug resistance in the environment and the community. In this review, we present current knowledge regarding the spread of carbapenemase-producing isolates in different aquatic environments, which may help the implementation of control and prevention strategies against the spread of such dangerous resistant agents in the environment.202133895415
9928170.9999The emergence and implications of metallo-beta-lactamases in Gram-negative bacteria. The increase in Gram-negative broad-spectrum antibiotic resistance is worrisome, particularly as there are few, if any, ''pipeline'' antimicrobial agents possessing suitable activity against Pseudomonas spp. or Acinetobacter spp. The increase in resistance will be further enhanced by the acquisition of metallo-beta-lactamase (MBL) genes that can potentially confer broad-spectrum beta-lactam resistance. These genes encode enzymes that can hydrolyse all classes of beta-lactams and the activity of which cannot be neutralised by beta-lactamase inhibitors. MBL genes are often associated with aminoglycoside resistant genes and thus bacteria that possess MBL genes are often co-resistant to aminoglycosides, further compromising therapeutic regimes. Both types of genes can be found as gene cassettes carried by integrons that in turn are embedded within transposons providing a highly ambulatory genetic element. The dissemination of MBL genes is typified by the spread of blaVIM-2, believed to originate from a Portuguese patient in 1995, and is now present in over 20 counties. The increase in international travel is likely to be a contributory factor for the ascendancy of mobile MBL genes as much as the mobility among individual bacteria. Fitness, acquisition and host dependency are key areas that need to be addressed to enhance our understanding of how antibiotic resistance spreads. There is also a pressing need for new, and hopefully novel, compounds active against pan-resistant Gram-negative bacteria--a growing problem that needs to be addressed by both government and industry.200516209700
4861180.9999The 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
1547190.9999The 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