A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques. - Related Documents




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488801.0000A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques. Infectious disease outbreaks have caused thousands of deaths and hospitalizations, along with severe negative global economic impacts. Among these, infections caused by antimicrobial-resistant microorganisms are a major growing concern. The misuse and overuse of antimicrobials have resulted in the emergence of antimicrobial resistance (AMR) worldwide. Carbapenem-resistant Enterobacterales (CRE) are among the bacteria that need urgent attention globally. The emergence and spread of carbapenem-resistant bacteria are mainly due to the rapid dissemination of genes that encode carbapenemases through horizontal gene transfer (HGT). The rapid dissemination enables the development of host colonization and infection cases in humans who do not use the antibiotic (carbapenem) or those who are hospitalized but interacting with environments and hosts colonized with carbapenemase-producing (CP) bacteria. There are continuing efforts to characterize and differentiate carbapenem-resistant bacteria from susceptible bacteria to allow for the appropriate diagnosis, treatment, prevention, and control of infections. This review presents an overview of the factors that cause the emergence of AMR, particularly CRE, where they have been reported, and then, it outlines carbapenemases and how they are disseminated through humans, the environment, and food systems. Then, current and emerging techniques for the detection and surveillance of AMR, primarily CRE, and gaps in detection technologies are presented. This review can assist in developing prevention and control measures to minimize the spread of carbapenem resistance in the human ecosystem, including hospitals, food supply chains, and water treatment facilities. Furthermore, the development of rapid and affordable detection techniques is helpful in controlling the negative impact of infections caused by AMR/CRE. Since delays in diagnostics and appropriate antibiotic treatment for such infections lead to increased mortality rates and hospital costs, it is, therefore, imperative that rapid tests be a priority.202337374993
488910.9999The Challenge of Overcoming Antibiotic Resistance in Carbapenem-Resistant Gram-Negative Bacteria: "Attack on Titan". The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multidrug-resistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance genes, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.202337630472
488720.9999Mechanisms of Bacterial Drug Resistance with Special Emphasis on Phenotypic and Molecular Characterization of Extended Spectrum Beta-lactamase. Antibiotics are designed to effectively treat bacterial infections while minimizing harm to the human body. They work by targeting specific components of bacteria or by disrupting essential processes such as cell wall synthesis, membrane function, protein production, and metabolic pathways. However, the misuse and overuse of antibiotics have led to the emergence of drug resistance in humans, animals, and agriculture, contributing to the global spread of this problem. Drug resistance can be either innate or acquired, with acquired resistance involving changes in the bacterial chromosomes or transferable elements. Bacterial species employ various mechanisms of drug resistance, including modifying the antibiotic targets, inactivating the drug, reducing uptake or increasing efflux, overexpressing the target, utilizing alternative pathways, and forming biofilms. One significant concern in the realm of drug resistance revolves around the emergence and proliferation of extended-spectrum beta-lactamases (ESBLs), a gene that is found in most gram-negative bacteria, primarily carried by Escherichia coli and Klebsiella pneumoniae in healthcare settings. ESBL-mediated resistance poses challenges for diagnosis, treatment, infection control, and antibiotic stewardship. Accurate detection of ESBL genes is crucial, and phenotypic methods are commonly used for initial screening. However, these methods have limitations, and confirmatory molecular techniques such as PCR and DNA sequencing are employed to accurately identify ESBL genes. Despite the significant global concerns surrounding ESBLs, they have spread worldwide, mainly facilitated by healthcare settings, inappropriate antimicrobial use, and host susceptibility. Addressing this issue requires implementing comprehensive measures, including enhanced surveillance, strict infection control practices, antibiotic stewardship programs, rapid diagnostic methods, alternative therapies, public education initiatives, and research focused on developing new drugs. Furthermore, collaboration among the healthcare, public health, and research sectors is pivotal in effectively combating the escalating threat posed by ESBL-mediated resistance. Antibiotics have revolutionized medical care by effectively treating bacterial infections. However, the emergence of ESBL gene resistance poses a global challenge that requires an integrated approach to prevent a threatening future.202438700878
488530.9999A Review of the Diagnostic Approaches for the Detection of Antimicrobial Resistance, Including the Role of Biosensors in Detecting Carbapenem Resistance Genes. Antimicrobial resistance (AMR) is a rapidly growing global concern resulting from the overuse of antibiotics in both agricultural and clinical settings, the lack of surveillance for resistant bacteria, and the low quality of some available antimicrobial agents. Resistant pathogens are no longer susceptible to common clinical antimicrobials, which decreases the effectiveness of medicines used to treat infections caused by these organisms. Carbapenems are an important class of antibiotics due to their broad-spectrum effectiveness in treating infections caused by Gram-positive and Gram-negative organisms. Carbapenem-resistant bacteria have been found not only in healthcare but also in the environment and food supply chain, where they have the potential to spread to pathogens and infect humans and animals. Current methods of detecting AMR genes are expensive and time-consuming. While these methods, like polymerase chain reactions or whole-genome sequencing, are considered the "gold standard" for diagnostics, the development of inexpensive, rapid diagnostic assays is necessary for effective AMR detection and management. Biosensors have shown potential for success in diagnostic testing due to their ease of use, inexpensive materials, rapid results, and portable nature. Biosensors can be combined with nanomaterials to produce sensitive and easily interpretable results. This review presents an overview of carbapenem resistance, current and emerging detection methods of antimicrobial resistance, and the application of biosensors for rapid diagnostic testing for bacterial resistance.202540725449
661640.9999The menace of colistin resistance across globe: Obstacles and opportunities in curbing its spread. Colistin-resistance in bacteria is a big concern for public health, since it is a last resort antibiotic to treat infectious diseases of multidrug resistant and carbapenem resistant Gram-negative pathogens in clinical settings. The emergence of colistin resistance in aquaculture and poultry settings has escalated the risks associated with colistin resistance in environment as well. The staggering number of reports pertaining to the rise of colistin resistance in bacteria from clinical and non-clinical settings is disconcerting. The co-existence of colistin resistant genes with other antibiotic resistant genes introduces new challenges in combatting antimicrobial resistance. Some countries have banned the manufacture, sale and distribution of colistin and its formulations for food producing animals. However, to tackle the issue of antimicrobial resistance, a one health approach initiative, inclusive of human, animal, and environmental health needs to be developed. Herein, we review the recent reports in colistin resistance in bacteria of clinical and non-clinical settings, deliberating on the new findings obtained regarding the development of colistin resistance. This review also discusses the initiatives implemented globally in mitigating colistin resistance, their strength and weakness.202336812837
661750.9999Mechanisms in colistin-resistant superbugs transmissible from veterinary, livestock and animal food products to humans. In the era of antibiotic resistance, where multidrug-resistant (MDR), extensively drug resistant (XDR), and pan-drug resistant (PDR) Gram-negative infections are prevalent, it is crucial to identify the primary sources of antibiotic resistance, understand resistant mechanisms, and develop strategies to combat these mechanisms. The emergence of resistance to last-resort antibiotics like colistin has sparked a war between humanity and resistant bacteria, leaving humanity struggling to find effective countermeasures. Although colistin is used as a highly toxic antibiotic in infections that are not treated with routine antibiotics, its widespread use in animal breeding and veterinary medicine has contributed to the spread of colistin-resistant bacteria, plasmid-borne colistin resistance genes (mcr), and antibiotic residues in livestock and animal-derived foods. These sources can potentially transmit colistin resistance to humans through various routes. Therefore, managing the use of colistin in livestock and animal foods, implementing strict monitoring, and establishing guidelines for its proper use are essential to prevent the escalation of colistin resistance. This review article discusses the latest mechanisms of colistin antibiotic resistance, particularly biofilm production as a public health threat, the livestock and animal food sources of this resistance, and the routes of transmission to humans.202540386099
488660.9999Molecular diagnostics for genotypic detection of antibiotic resistance: current landscape and future directions. Antimicrobial resistance (AMR) among bacteria is an escalating public health emergency that has worsened during the COVID-19 pandemic. When making antibiotic treatment decisions, clinicians rely heavily on determination of antibiotic susceptibility or resistance by the microbiology laboratory, but conventional methods often take several days to identify AMR. There are now several commercially available molecular methods that detect antibiotic resistance genes within hours rather than days. While these methods have limitations, they offer promise for optimizing treatment and patient outcomes, and reducing further emergence of AMR. This review provides an overview of commercially available genotypic assays that detect individual resistance genes and/or resistance-associated mutations in a variety of specimen types and discusses how clinical outcomes studies may be used to demonstrate clinical utility of such diagnostics.202336816746
489070.9999Understanding of Colistin Usage in Food Animals and Available Detection Techniques: A Review. Progress in the medical profession is determined by the achievements and effectiveness of new antibiotics in the treatment of microbial infections. However, the development of multiple-drug resistance in numerous bacteria, especially Gram-negative bacteria, has limited the treatment options. Due to this resistance, the resurgence of cyclic polypeptide drugs like colistin remains the only option. The drug, colistin, is a well-known growth inhibitor of Gram-negative bacteria like Acinetobacter baumanni, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Technological advancements have uncovered the role of the mcr-1(mobilized colistin resistance) gene, which is responsible for the development of resistance in Gram-negative bacteria, which make them distinct from other bacteria without this gene. Additionally, food animals have been determined to be the reservoir for colistin resistance microbes, from which they spread to other hosts. Due to the adverse effects of colistin, many developed countries have prohibited its usage in animal foods, but developing countries are still using colistin in animal food production, thereby imposing a major risk to the public health. Therefore, there is a need for implementation of sustainable measures in livestock farms to prevent microbial infection. This review highlights the negative effects (increased resistance) of colistin consumption and emphasizes the different approaches used for detecting colistin in animal-based foods as well as the challenges associated with its detection.202033081121
487480.9999Mobilized colistin resistance (mcr) genes from 1 to 10: a comprehensive review. At the present time, the polymyxin antibiotic colistin is considered a last-line treatment option for severe human infections caused by multi-drug and carbapenem-resistant Gram-negative bacteria. Lately, the vast spread of colistin resistance among bacteria has got great attention worldwide due to its significant role as the last refuge in treating diseases caused by the resistant infectious agents. Therefore, the discovery of plasmid-mediated mobile colistin resistance (mcr) genes raised global public health concerns as they can spread by horizontal transfer and have chances of global dissemination. To date, ten slightly different variants of the mcr-1 gene (mcr-1 to mcr-10) have been identified in different bacteria isolated from animals, foods, farms, humans, and the environment. Therefore, the issue of mcr spread is growing and worsening day after day. In this backdrop, the current article presents an overview of mcr variants, their spread, and the resistance mechanisms they confer. Hence, this paper will advance our knowledge about colistin resistance while supporting the efforts toward better stewardship and proper usage of antimicrobials.202133839987
661390.9998Approaches for characterizing and tracking hospital-associated multidrug-resistant bacteria. Hospital-associated infections are a major concern for global public health. Infections with antibiotic-resistant pathogens can cause empiric treatment failure, and for infections with multidrug-resistant bacteria which can overcome antibiotics of "last resort" there exists no alternative treatments. Despite extensive sanitization protocols, the hospital environment is a potent reservoir and vector of antibiotic-resistant organisms. Pathogens can persist on hospital surfaces and plumbing for months to years, acquire new antibiotic resistance genes by horizontal gene transfer, and initiate outbreaks of hospital-associated infections by spreading to patients via healthcare workers and visitors. Advancements in next-generation sequencing of bacterial genomes and metagenomes have expanded our ability to (1) identify species and track distinct strains, (2) comprehensively profile antibiotic resistance genes, and (3) resolve the mobile elements that facilitate intra- and intercellular gene transfer. This information can, in turn, be used to characterize the population dynamics of hospital-associated microbiota, track outbreaks to their environmental reservoirs, and inform future interventions. This review provides a detailed overview of the approaches and bioinformatic tools available to study isolates and metagenomes of hospital-associated bacteria, and their multi-layered networks of transmission.202133582841
4332100.9998Development and transmission of antimicrobial resistance among Gram-negative bacteria in animals and their public health impact. Gram-negative bacteria are known to cause severe infections in both humans and animals. Antimicrobial resistance (AMR) in Gram-negative bacteria is a major challenge in the treatment of clinical infections globally due to the propensity of these organisms to rapidly develop resistance against antimicrobials in use. In addition, Gram-negative bacteria possess highly efficient mechanisms through which the AMR can be disseminated between pathogenic and commensal bacteria of the same or different species. These unique traits of Gram-negative bacteria have resulted in evolution of Gram-negative bacterial strains demonstrating resistance to multiple classes of antimicrobials. The evergrowing resistance issue has not only resulted in limitation of treatment options but also led to increased treatment costs and mortality rates in humans and animals. With few or no new antimicrobials in production to combat severe life-threatening infections, AMR has been described as the one of the most severe, long-term threats to human health. Aside from overuse and misuse of antimicrobials in humans, another factor that has exacerbated the emergence of AMR in Gram-negative bacteria is the veterinary use of antimicrobials that belong to the same classes considered to be critically important for treating serious life-threatening infections in humans. Despite the fact that development of AMR dates back to before the introduction of antimicrobials, the recent surge in the resistance towards all available critically important antimicrobials has emerged as a major public health issue. This review thus focuses on discussing the development, transmission and public health impact of AMR in Gram-negative bacteria in animals.201728258227
6614110.9998Whole-Genome Sequencing of Pathogenic Bacteria-New Insights into Antibiotic Resistance Spreading. In recent years, the acquisition of antimicrobial resistance (AMR) by both pathogenic and opportunistic bacteria has become a major problem worldwide, which was already noticed as a global healthcare threat by the World Health Organization [...].202134946225
4873120.9998Farm animals and aquaculture: significant reservoirs of mobile colistin resistance genes. Colistin resistance has attracted substantial attention after colistin was considered as a last-resort drug for the treatment of infections caused by carbapenem-resistant and/or multidrug-resistant (MDR) Gram-negative bacteria in clinical settings. However, with the discovery of highly mobile colistin resistance (mcr) genes, colistin resistance has become an increasingly urgent issue worldwide. Despite many reviews, which summarized the prevalence, mechanisms, and structures of these genes in bacteria of human and animal origin, studies on the prevalence of mobile colistin resistance genes in aquaculture and their transmission between animals and humans remain scarce. Herein, we review recent reports on the prevalence of colistin resistance genes in animals, especially wildlife and aquaculture, and their possibility of transmission to humans via the food chain. This review also gives some insights into the routine surveillance, changing policy and replacement of polymyxins by polymyxin derivatives, molecular inhibitors, and traditional Chinese medicine to tackle colistin resistance.202032114703
6620130.9998The growing burden of antimicrobial resistance. Since the first usage of antimicrobials, the burden of resistance among bacteria has progressively increased and has accelerated within the last 10 years. Antibiotic resistance genes were present at very low levels prior to the introduction of antibiotics and it is largely the selective pressure of antibiotic use and the resulting exposure of bacteria, not only in humans but also in companion and food animals and the environment, which has caused the rise. The increasing mobility across the globe of people, food and animals is another factor. Examples of this are the international pandemic of different genotypes of CTX-M extended-spectrum beta-lactamases (particularly CTX-M-14 and -15) and the emergence of the carbapenemase KPC-1 in both the USA and Israel. This review details examples of both the emergence and dissemination through different genetic routes, both direct and indirect selective pressure, of significance resistance in Staphylococcus aureus, Enterococcus species, Enterobacteriaceae and Pseudomonas/Acinetobacter. The response made by society to reduce resistance involves surveillance, reduced usage, improved infection control and the introduction of new antimicrobial agents. Although efforts are being made in all these areas, there is an urgent need to increase the effectiveness of these interventions or some bacterial infections will become difficult if not impossible to treat reliably.200818684701
4872140.9998A Review on Colistin Resistance: An Antibiotic of Last Resort. Antibiotic resistance has emerged as a significant global public health issue, driven by the rapid adaptation of microorganisms to commonly prescribed antibiotics. Colistin, previously regarded as a last-resort antibiotic for treating infections caused by Gram-negative bacteria, is increasingly becoming resistant due to chromosomal mutations and the acquisition of resistance genes carried by plasmids, particularly the mcr genes. The mobile colistin resistance gene (mcr-1) was first discovered in E. coli from China in 2016. Since that time, studies have reported different variants of mcr genes ranging from mcr-1 to mcr-10, mainly in Enterobacteriaceae from various parts of the world, which is a major concern for public health. The co-presence of colistin-resistant genes with other antibiotic resistance determinants further complicates treatment strategies and underscores the urgent need for enhanced surveillance and antimicrobial stewardship efforts. Therefore, understanding the mechanisms driving colistin resistance and monitoring its global prevalence are essential steps in addressing the growing threat of antimicrobial resistance and preserving the efficacy of existing antibiotics. This review underscores the critical role of colistin as a last-choice antibiotic, elucidates the mechanisms of colistin resistance and the dissemination of resistant genes, explores the global prevalence of mcr genes, and evaluates the current detection methods for colistin-resistant bacteria. The objective is to shed light on these key aspects with strategies for combating the growing threat of resistance to antibiotics.202438674716
4853150.9998Success and Challenges Associated with Large-Scale Collaborative Surveillance for Carbapenemase Genes in Gram-Negative Bacteria. The emergence and spread of antimicrobial resistance, especially in Gram-negative bacteria, has led to significant morbidity and increased cost of health care. Large surveillance studies such as the one performed by the Antibiotic Resistance Laboratory Network are immensely valuable in understanding the scope of resistance mechanisms, especially among carbapenemase-producing Gram-negative bacteria. However, the routine laboratory detection of carbapenemases in these bacteria remains challenging and requires further optimization.202234930024
4856160.9998An Overview on Phenotypic and Genotypic Characterisation of Carbapenem-Resistant Enterobacterales. Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected individuals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population; however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.202236422214
6624170.9998Water as a Source of Antimicrobial Resistance and Healthcare-Associated Infections. Healthcare-associated infections (HAIs) are one of the most common patient complications, affecting 7% of patients in developed countries each year. The rise of antimicrobial resistant (AMR) bacteria has been identified as one of the biggest global health challenges, resulting in an estimated 23,000 deaths in the US annually. Environmental reservoirs for AMR bacteria such as bed rails, light switches and doorknobs have been identified in the past and addressed with infection prevention guidelines. However, water and water-related devices are often overlooked as potential sources of HAI outbreaks. This systematic review examines the role of water and water-related devices in the transmission of AMR bacteria responsible for HAIs, discussing common waterborne devices, pathogens, and surveillance strategies. AMR strains of previously described waterborne pathogens including Pseudomonas aeruginosa, Mycobacterium spp., and Legionella spp. were commonly isolated. However, methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacteriaceae that are not typically associated with water were also isolated. Biofilms were identified as a hot spot for the dissemination of genes responsible for survival functions. A limitation identified was a lack of consistency between environmental screening scope, isolation methodology, and antimicrobial resistance characterization. Broad universal environmental surveillance guidelines must be developed and adopted to monitor AMR pathogens, allowing prediction of future threats before waterborne infection outbreaks occur.202032824770
4185180.9998Containment of antimicrobial resistance due to use of antimicrobial agents in animals intended for food: WHO perspective. The use of antimicrobial agents in humans and food-producing animals has important consequences for human and animal health, as it can lead to the development of resistant bacteria (pathogens and/or commensals with resistance genes). Moreover, resistant bacteria in animals can be transferred to people--usually through the consumption of food, but also through direct contact with food-producing animals or through environmental spread. Ultimately, this can result in human infections with bacteria that are resistant to antimicrobial agents and that can therefore be difficult or impossible to cure. Of special concern is resistance to antimicrobial agents classified by the World Health Organization (WHO) as critically important for human medicine, such as fluoroquinolones, third- and fourth-generation cephalosporins, and macrolides. WHO encourages the agricultural, food, veterinary and health sectors to work together to eliminate the burden of antimicrobial resistance arising from the use of antimicrobial agents in food-producing animals. Joint efforts should be made to reduce the inappropriate use of antimicrobial agents (e.g. the use of antimicrobials as growth promoters) and limit the spread of bacteria resistant to antimicrobial agents. WHO will continueto address this issue in conjunction with the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health, the animal health/production industry and other important stakeholders. It will also continue to enhance the capacity of its Member States (through training courses and sentinel studies), particularly developing countries, to conduct integrated surveillance of antimicrobial use and resistance, to carry out risk assessments to support the selection of risk management options and to implement strategies for the containment of antimicrobial resistance.201222849282
4877190.9998Carbapenemase-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