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250000.9957The crisis of carbapenemase-mediated carbapenem resistance across the human-animal-environmental interface in India. Carbapenems are the decision-making antimicrobials used to combat severe Gram-negative bacterial infections in humans. Carbapenem resistance poses a potential public health emergency, especially in developing countries such as India, accounting for high morbidity, mortality, and healthcare cost. Emergence and transmission of plasmid-mediated "big five" carbapenemase genes including KPC, NDM, IMP, VIM and OXA-48-type among Gram-negative bacteria is spiralling the issue. Carbapenemase-producing carbapenem-resistant organisms (CP-CRO) cause multi- or pan-drug resistance by co-harboring several antibiotic resistance determinants. In addition of human origin, animals and even environmental sites are also the reservoir of CROs. Spillage in food-chains compromises food safety and security and increases the chance of cross-border transmission of these superbugs. Metallo-β-lactamases, mainly NDM-1 producing CROs, are commonly shared between human, animal and environmental interfaces worldwide, including in India. Antimicrobial resistance (AMR) surveillance using the One Health approach has been implemented in Europe, the United-Kingdom and the United-States to mitigate the crisis. This concept is still not implemented in most developing countries, including India, where the burden of antibiotic-resistant bacteria is high. Lack of AMR surveillance in animal and environmental sectors underestimates the cumulative burden of carbapenem resistance resulting in the silent spread of these superbugs. In-depth indiscriminate AMR surveillance focusing on carbapenem resistance is urgently required to develop and deploy effective national policies for preserving the efficacy of carbapenems as last-resort antibiotics in India. Tracking and mapping of international high-risk clones are pivotal for containing the global spread of CP-CRO.202336241158
660610.9957Comprehensive analysis of antimicrobial resistance in the Southwest Indian Ocean: focus on WHO critical and high priority pathogens. The spread of antimicrobial resistance (AMR) is a major global concern, and the islands of the Southwest Indian Ocean (SWIO) are not exempt from this phenomenon. As strategic crossroads between Southern Africa and the Indian subcontinent, these islands are constantly threatened by the importation of multidrug-resistant bacteria from these regions. In this systematic review, our aim was to assess the epidemiological situation of AMR in humans in the SWIO islands, focusing on bacterial species listed as priority by the World Health Organization. Specifically, we examined Enterobacterales, Acinetobacter spp., Pseudomonas spp. resistant to carbapenems, and Enterococcus spp. resistant to vancomycin. Our main objectives were to map the distribution of these resistant bacteria in the SWIO islands and identify the genes involved in their resistance mechanisms. We conducted literature review focusing on Comoros, Madagascar, Maldives, Mauritius, Mayotte, Reunion Island, Seychelles, Sri Lanka, and Zanzibar. Our findings revealed a growing interest in the investigation of these pathogens and provided evidence of their active circulation in many of the territories investigated. However, we also identified disparities in terms of data availability between the targeted bacteria and among the different territories, emphasizing the need to strengthen collaborative efforts to establish an efficient regional surveillance network.202438628847
252520.9956Review of antimicrobial resistance surveillance programmes in livestock and meat in EU with focus on humans. OBJECTIVES: In this review, we describe surveillance programmes reporting antimicrobial resistance (AMR) and resistance genes in bacterial isolates from livestock and meat and compare them with those relevant for human health. METHODS: Publications on AMR in European countries were assessed. PubMed was reviewed and AMR monitoring programmes were identified from reports retrieved by Internet searches and by contacting national authorities in EU/European Economic Area (EEA) member states. RESULTS: Three types of systems were identified: EU programmes, industry-funded supranational programmes and national surveillance systems. The mandatory EU-financed programme has led to some harmonization in national monitoring and provides relevant information on AMR and extended-spectrum β-lactamase/AmpC- and carbapenemase-producing bacteria. At the national level, AMR surveillance systems in livestock apply heterogeneous sampling, testing and reporting modalities, resulting in results that cannot be compared. Most reports are not publicly available or are written in a local language. The industry-funded monitoring systems undertaken by the Centre Européen d'Etudes pour la Santé Animale (CEESA) examines AMR in bacteria in food-producing animals. CONCLUSIONS: Characterization of AMR genes in livestock is applied heterogeneously among countries. Most antibiotics of human interest are included in animal surveillance, although results are difficult to compare as a result of lack of representativeness of animal samples. We suggest that EU/EEA countries provide better uniform AMR monitoring and reporting in livestock and link them better to surveillance systems in humans. Reducing the delay between data collection and publication is also important to allow prompt identification of new resistance patterns.201828970159
485130.9956A 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
251740.9955The 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
661650.9955The 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
249360.9955Multidrug-resistant hypervirulent Klebsiella pneumoniae: an evolving superbug. Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) combines high pathogenicity with multidrug resistance to become a new superbug. MDR-hvKP reports continue to emerge, shattering the perception that hypervirulent K. pneumoniae (hvKP) strains are antibiotic sensitive. Patients infected with MDR-hvKP strains have been reported in Asia, particularly China. Although hvKP can acquire drug resistance genes, MDR-hvKP seems to be more easily transformed from classical K. pneumoniae (cKP), which has a strong gene uptake ability. To better understand the biology of MDR-hvKP, this review discusses the virulence factors, resistance mechanisms, formation pathways, and identification of MDR-hvKP. Given their destructive and transmissible potential, continued surveillance of these organisms and enhanced control measures should be prioritized.202540135944
669170.9955The antimicrobial resistance monitoring and research (ARMoR) program: the US Department of Defense response to escalating antimicrobial resistance. Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration, the Antimicrobial Resistance Monitoring and Research Program, to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, bacteria containing AMR-encoding genes are increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program.201424795331
488880.9955A 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
501290.9954Extended-spectrum beta-lactamases-producing gram-negative bacteria in companion animals: action is clearly warranted! Extended-spectrum beta-lactamases (ESBL)-producing Gram-negative bacteria pose a serious threat to Public Health in human medicine as well as increasingly in the veterinary context worldwide. Several studies reported the transmission of zoonotic multidrug resistant bacteria between food-producing animals and humans, whilst the contribution of companion animals to this scenario is rather unknown. Within the last decades a change in the social role of companion animals has taken place, resulting in a very close contact between owners and their pets. As a consequence, humans may obtain antimicrobial resistant bacteria or the corresponding resistance genes not only from food-producing animals but also via close contact to their pets.This may give rise to bacterial infections with limited therapeutic options and an increased risk of treatment failure. As beta-lactams constitute one of the most important groups of antimicrobial agents in veterinary medicine, retaliatory actions in small animal and equine practices are urgently needed. This review addresses the increasing burden of extended-spectrum beta-lactam resistance among Enterobacteriaceae isolated from companion animals. It should emphasize the urgent need for the implementation of antibiotic stewardship as well as surveillance and monitoring programs of multi resistant bacteria in particular in view of new putative infection cycles between humans and their pets.201121462862
9075100.9954CamPype: an open-source workflow for automated bacterial whole-genome sequencing analysis focused on Campylobacter. BACKGROUND: The rapid expansion of Whole-Genome Sequencing has revolutionized the fields of clinical and food microbiology. However, its implementation as a routine laboratory technique remains challenging due to the growth of data at a faster rate than can be effectively analyzed and critical gaps in bioinformatics knowledge. RESULTS: To address both issues, CamPype was developed as a new bioinformatics workflow for the genomics analysis of sequencing data of bacteria, especially Campylobacter, which is the main cause of gastroenteritis worldwide making a negative impact on the economy of the public health systems. CamPype allows fully customization of stages to run and tools to use, including read quality control filtering, read contamination, reads extension and assembly, bacterial typing, genome annotation, searching for antibiotic resistance genes, virulence genes and plasmids, pangenome construction and identification of nucleotide variants. All results are processed and resumed in an interactive HTML report for best data visualization and interpretation. CONCLUSIONS: The minimal user intervention of CamPype makes of this workflow an attractive resource for microbiology laboratories with no expertise in bioinformatics as a first line method for bacterial typing and epidemiological analyses, that would help to reduce the costs of disease outbreaks, or for comparative genomic analyses. CamPype is publicly available at https://github.com/JoseBarbero/CamPype .202337474912
5008110.9954Genetic diversity and risk factors for the transmission of antimicrobial resistance across human, animals and environmental compartments in East Africa: a review. BACKGROUND: The emergence and spread of antimicrobial resistance (AMR) present a challenge to disease control in East Africa. Resistance to beta-lactams, which are by far the most used antibiotics worldwide and include the penicillins, cephalosporins, monobactams and carbapenems, is reducing options for effective control of both Gram-positive and Gram-negative bacteria. The World Health Organization, Food and Agricultural Organization and the World Organization for Animal Health have all advocated surveillance of AMR using an integrated One Health approach. Regional consortia also have strengthened collaboration to address the AMR problem through surveillance, training and research in a holistic and multisectoral approach. This review paper contains collective information on risk factors for transmission, clinical relevance and diversity of resistance genes relating to extended-spectrum beta-lactamase-producing (ESBL) and carbapenemase-producing Enterobacteriaceae, and Methicillin-resistant Staphylococcus aureus (MRSA) across the human, animal and environmental compartments in East Africa. MAIN BODY: The review of the AMR literature (years 2001 to 2019) was performed using search engines such as PubMed, Scopus, Science Direct, Google and Web of Science. The search terms included 'antimicrobial resistance and human-animal-environment', 'antimicrobial resistance, risk factors, genetic diversity, and human-animal-environment' combined with respective countries of East Africa. In general, the risk factors identified were associated with the transmission of AMR. The marked genetic diversity due to multiple sequence types among drug-resistant bacteria and their replicon plasmid types sourced from the animal, human and environment were reported. The main ESBL, MRSA and carbapenem related genes/plasmids were the (bla)CTX-Ms (45.7%), SCCmec type III (27.3%) and IMP types (23.8%), respectively. CONCLUSION: The high diversity of the AMR genes suggests there may be multiple sources of resistance bacteria, or the possible exchange of strains or a flow of genes amongst different strains due to transfer by mobile genetic elements. Therefore, there should be harmonized One Health guidelines for the use of antibiotics, as well as regulations governing their importation and sale. Moreover, the trend of ESBLs, MRSA and carbapenem resistant (CAR) carriage rates is dynamic and are on rise over time period, posing a public health concern in East Africa. Collaborative surveillance of AMR in partnership with regional and external institutions using an integrated One Health approach is required for expert knowledge and technology transfer to facilitate information sharing for informed decision-making.202032762743
5110120.9954Surveillance of carbapenem-resistant organisms using next-generation sequencing. The genomic data generated from next-generation sequencing (NGS) provides nucleotide-level resolution of bacterial genomes which is critical for disease surveillance and the implementation of prevention strategies to interrupt the spread of antimicrobial resistance (AMR) bacteria. Infection with AMR bacteria, including Gram-negative Carbapenem-Resistant Organisms (CRO), may be acute and recurrent-once they have colonized a patient, they are notoriously difficult to eradicate. Through phylogenetic tools that assess the single nucleotide polymorphisms (SNPs) within a pathogen genome dataset, public health scientists can estimate the genetic identity between isolates. This information is used as an epidemiologic proxy of a putative outbreak. Pathogens with minimal to no differences in SNPs are likely to be the same strain attributable to a common source or transmission between cases. These genomic comparisons enhance public health response by prompting targeted intervention and infection control measures. This methodology overview demonstrates the utility of phenotypic and molecular assays, antimicrobial susceptibility testing (AST), NGS, publicly available genomics databases, and open-source bioinformatics pipelines for a tiered workflow to detect resistance genes and potential clusters of illness. These methods, when used in combination, facilitate a genomic surveillance workflow for detecting potential AMR bacterial outbreaks to inform epidemiologic investigations. Use of this workflow helps to target and focus epidemiologic resources to the cases with the highest likelihood of being related.202337255756
4855130.9954Carbapenem-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
5031140.9954Rapid Tracing of Resistance Plasmids in a Nosocomial Outbreak Using Optical DNA Mapping. Resistance to life-saving antibiotics increases rapidly worldwide, and multiresistant bacteria have become a global threat to human health. Presently, the most serious threat is the increasing spread of Enterobacteriaceae carrying genes coding for extended spectrum β-lactamases (ESBL) and carbapenemases on highly mobile plasmids. We here demonstrate how optical DNA maps of single plasmids can be used as fingerprints to trace plasmids, for example, during resistance outbreaks. We use the assay to demonstrate a potential transmission route of an ESBL-carrying plasmid between bacterial strains/species and between patients, during a polyclonal outbreak at a neonatal ward at Sahlgrenska University Hospital (Gothenburg, Sweden). Our results demonstrate that optical DNA mapping is an easy and rapid method for detecting the spread of plasmids mediating resistance. With the increasing prevalence of multiresistant bacteria, diagnostic tools that can aid in solving ongoing routes of transmission, in particular in hospital settings, will be of paramount importance.201627627201
6614150.9953Whole-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
6624160.9953Water 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
6615170.9953Is Africa ready for mobile colistin resistance threat? Antimicrobial resistance is a growing public health problem and a threat to effective treatment and prevention of an array of infections caused by bacteria. Africa is already faced with many socio-economic and health crises. Many countries in Africa can seldom boast of a standardized health care facility comparable to those in developed countries. Yet, the non-therapeutic use of COL has been banned in developed countries. However, in Africa, except for South Africa, COL is an over-the-counter (OTC) medication sold and dispensed by non-professionals/without a veterinarian's supervision. The ban of non-therapeutic COL in developed countries has proven to reduce the development of mobile colistin resistance (MCR) in humans and animals. The unregulated use of COL has been proven to select pathogenic and commensal bacteria resistance. A transmissible plasmid-mediated colistin determinant, mobile COL resistance (mcr) gene, which is rapidly transferred/acquired horizontally or laterally intra/inter-species/genera, has been reported. A highly promiscuous mobile genetic element like plasmids containing transposons, insertion sequences, and integrons aid the carriage/rapid transfer and acquisition of these mcr genes. Hence, we highlight the danger posed by escalating colistin (COL) resistance in the continent and the impetus to halt the indiscriminate and non-therapeutic use of COL to protect public health.202134377360
2492180.9953Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention. Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.202235979498
2511190.9953Klebsiella 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