Cracking the Code: Unveiling the Diversity of Carbapenem-Resistant Klebsiella pneumoniae Clones in the Arabian Peninsula through Genomic Surveillance. - Related Documents




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183301.0000Cracking the Code: Unveiling the Diversity of Carbapenem-Resistant Klebsiella pneumoniae Clones in the Arabian Peninsula through Genomic Surveillance. The rise of antimicrobial resistance is a global challenge that requires a coordinated effort to address. In this study, we examined the genetic similarity of carbapenem-resistant Klebsiella pneumoniae (CRKP) in countries belonging to the Gulf Cooperation Council (GCC) to gain a better understanding of how these bacteria are spreading and evolving in the region. We used in silico genomic tools to investigate the occurrence and prevalence of different types of carbapenemases and their relationship to specific sequence types (STs) of CRKP commonly found in the region. We analyzed 720 publicly available genomes of multi-drug resistant K. pneumoniae isolates collected from six GCC countries between 2011 and 2020. Our findings showed that ST-14 and ST-231 were the most common STs, and 51.7% of the isolates carried bla(OXA-48-like) genes. Additionally, we identified rare carbapenemase genes in a small number of isolates. We observed a clonal outbreak of ST-231 in Oman, and four Saudi isolates were found to have colistin resistance genes. Our study offers a comprehensive overview of the genetic diversity and resistance mechanisms of CRKP isolates in the GCC region that could aid in developing targeted interventions to combat this pressing global issue.202337508177
186710.9998Plasmid diversity of Serratia marcescens and Klebsiella pneumoniae isolates involved in two carbapenem-resistant Enterobacteriaceae outbreaks in a Swiss hospital. This study investigates two distinct carbapenemase-producing Enterobacteriaceae outbreaks involving patients and contaminated sink traps at the University Hospital of Lausanne. It focuses on the diversity and transmission dynamics of plasmids carrying carbapenemase genes. Between 2022 and 2023, 57 carbapenem-resistant Klebsiella pneumoniae and Serratia marcescens isolates were collected and analyzed. Core-genome MLST confirmed genetic similarity among isolates, linking the outbreaks to sink trap contamination. DNA extraction, sequencing (MinION/Illumina MiSeq), and assembly were performed, followed by ARG screening and plasmid typing. Plasmids were annotated, clustered, and compared using core SNP distances and structural analyses. Known plasmids were identified through PLSDB database matching. Eight MLST types were identified in K. pneumoniae and one (ST356) in S. marcescens. Analysis of 52 bla-carrying plasmids revealed 22 plasmid clusters, including 6 bla(NDM-1) clusters in K. pneumoniae and 4 bla(KPC-2) clusters in S. marcescens. Plasmids showed close relatedness within and across patient and environmental isolates, with core SNP distances ranging from 0 to 18. Some bla(NDM-1) plasmids in K. pneumoniae clustered tightly, suggesting persistence and potential cross-contamination routes. The findings highlight sink traps as critical reservoirs for carbapenem-resistant Enterobacteriaceae and plasmids, promoting resistance gene spread across species. The observed plasmid diversity indicates transmission can occur independently of bacterial clonal spread, challenging traditional outbreak definitions. IMPORTANCE: This research is critical in addressing the growing threat of antibiotic resistance, driven by the spread of resistance genes through plasmids. Plasmids, which can transfer between different bacteria, play a major role in spreading multidrug resistance, posing a serious challenge to healthcare systems worldwide. By highlighting how plasmids can move independently of bacterial spread, this study reveals the complexity of resistance transmission. It also underscores the importance of environmental reservoirs, such as hospital sink traps, in harboring and spreading resistant bacteria. These findings emphasize the need for better monitoring of plasmids and targeted infection control measures to prevent the spread of resistance genes and protect the effectiveness of current antibiotics.202540396774
183220.9998Long-read sequencing reveals genomic diversity and associated plasmid movement of carbapenemase-producing bacteria in a UK hospital over 6 years. Healthcare-associated infections (HCAIs) affect the most vulnerable people in society and are increasingly difficult to treat in the face of mounting antimicrobial resistance (AMR). Routine surveillance represents an effective way of understanding the circulation and burden of bacterial resistance and transmission in hospital settings. Here, we used whole-genome sequencing (WGS) to retrospectively analyse carbapenemase-producing Gram-negative bacteria from a single hospital in the UK over 6 years (n=165). We found that the vast majority of isolates were either hospital-onset (HAI) or HCAI. Most carbapenemase-producing organisms were carriage isolates, with 71 % isolated from screening (rectal) swabs. Using WGS, we identified 15 species, the most common being Escherichia coli and Klebsiella pneumoniae. Only one significant clonal outbreak occurred during the study period and involved a sequence type (ST)78 K. pneumoniae carrying bla (NDM-1) on an IncFIB/IncHI1B plasmid. Contextualization with public data revealed little evidence of this ST outside of the study hospital, warranting ongoing surveillance. Carbapenemase genes were found on plasmids in 86 % of isolates, the most common types being bla (NDM)- and bla (OXA)-type alleles. Using long-read sequencing, we determined that approximately 30 % of isolates with carbapenemase genes on plasmids had acquired them via horizontal transmission. Overall, a national framework to collate more contextual genomic data, particularly for plasmids and resistant bacteria in the community, is needed to better understand how carbapenemase genes are transmitted in the UK.202337405394
183430.9998Multiple host colonization and differential expansion of multidrug-resistant ST25-Acinetobacter baumannii clades. The Acinetobacter baumannii clonal lineage ST25 has been identified in humans and animals and found associated with outbreaks globally. To highlight possible similarities among ST25 A. baumannii of animal and human origins and to gather clues on the dissemination and evolution of the ST25 lineage, we conducted a phylogenetic analysis on n = 106 human and n = 35 animal A. baumannii ST25 genomes, including 44 sequenced for this study. Resistance genes and their genetic background were analyzed, as well. ST25 genomes are clustered into four clades: two are widespread in South America, while the other two are largely distributed in Europe, Asia and America. One particular clade was found to include the most recent strains and the highest number of acquired antibiotic resistance genes. OXA-23-type carbapenemase was the most common. Other resistance genes such as bla(NDM-1), bla(PER-7), and armA were found embedded in complex chromosomal regions present in human isolates. Genomic similarity among multidrug resistant ST25 isolates of either animal or human origin was revealed, suggesting cross-contaminations between the two sectors. Tracking the clonal complex ST25 between humans and animals should provide new insights into the mode of dissemination of these bacteria, and should help defining strategies for preserving global health.202338071225
157140.9998Klebsiella pneumoniae ST147 harboring bla(NDM-1), multidrug resistance and hypervirulence plasmids. The spread of hypervirulent (hv) and carbapenem-/multidrug-resistant Klebsiella pneumoniae is an emerging problem in healthcare settings. The New Delhi metallo-β-lactamase-1 (bla(NDM-1)) is found in Enterobacteriaceae including K. pneumoniae. The bla(NDM-1) is capable of hydrolyzing β-lactam antibiotics which are used for treatment of severe infections caused by multidrug-resistant Gram-negative bacteria. This is associated with the unacceptably high mortality rate in immunocompromised burn injury patients. This study reports on the characterization of bla(NDM-1) gene and virulence factors in hv carbapenem-/multidrug-resistant K. pneumoniae ST147 in the burns unit of a tertiary teaching hospital during routine surveillance. Two K. pneumoniae strains were obtained from wounds of burn-infected patients from May 2020 to July 2021. The hypervirulence genes and genetic context of the bla(NDM-1) gene and mobile genetic elements potentially involved in the transposition of the gene were analyzed. We identified a conserved genetic background and an IS26 and open reading frame flanking the bla(NDM-1) gene that could suggest its involvement in the mobilization of the gene. The plasmid harbored additional antibiotic resistance predicted regions that were responsible for resistance to almost all the routinely used antibiotics. To ensure the identification of potential outbreak strains during routine surveillance, investigations on resistance genes and their environment in relation to evolution are necessary for molecular epidemiology.IMPORTANCEData obtained from this study will aid in the prompt identification of disease outbreaks including evolving resistance and virulence of the outbreak bacteria. This will help establish and implement antimicrobial stewardship programs and infection prevention protocols in fragile health systems in countries with limited resources. Integration of molecular surveillance and translation of whole-genome sequencing in routine diagnosis will provide valuable data for control of infection. This study reports for the first time a high-risk clone K. pneumoniae ST147 with hypervirulence and multidrug-resistance features in Ghana.202438315028
190750.9997Nationwide surveillance of carbapenem-resistant Gram-negative pathogens in the Lebanese environment. Gram-negative ESKAPE pathogens with carbapenem resistance pose a significant health threat. Despite extensive research on the spread of these pathogens within Lebanese hospital settings, their emergence in environmental settings remains understudied. This study aimed to explore the environmental spread of carbapenem resistance among Gram-negative bacteria isolated from environmental samples in nine districts across Lebanon. A total of 250 samples were collected from wild animals, sewage, water, and soil between June 2022 and September 2023. Samples were streaked on MacConkey agar plates supplemented with 2 mg/L meropenem. Bacterial species were identified primarily using API20E. Antimicrobial susceptibility profiles were determined by the disk diffusion method and the Vitek 2 compact system. Meropenem-resistant Gram-negative bacteria were further characterized by whole-genome sequencing, and each of the bacterial species, sequence types, resistance genes, and plasmids was detected by sequence data analysis. We successfully isolated 130 carbapenem-resistant isolates from various samples, 67 of which belonged to the ESKAPE pathogens list and showed a multidrug-resistant (MDR) profile. The distribution of the latter was as follows: Escherichia coli (65.67%), Acinetobacter baumannii (16.42%), Pseudomonas aeruginosa (11.94%), and Klebsiella pneumoniae (5.97%). Several carbapenem resistance genes were detected, with a prevalence of blaNDM-5 in Escherichia coli and Klebsiella pneumoniae, blaIMP-1 and mexAB-OprM efflux pumps in Pseudomonas aeruginosa, and blaOXA-23 in Acinetobacter baumannii. Our findings revealed a widespread distribution of carbapenem-resistant ESKAPE bacteria in Lebanon, underscoring the significant public health risk posed by these pathogens. This highlights the urgent need to address the dissemination of antibiotic resistance in Lebanese environmental settings. IMPORTANCE: The emergence of antimicrobial resistance (AMR) extremely burdens public health and increases morbid and mortal threats in Lebanon. While the majority of the studies in our country target antimicrobial resistance in clinical settings, fewer studies focus on antimicrobial resistance dissemination in the environment. The significance of our research is that it sheds light on the environment as a less explored yet equally crucial sector in the spread of AMR. Here, we isolated carbapenemase-producing bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) that were categorized as multidrug resistant (MDR) from diverse environmental sources in multiple provinces across Lebanon. The finding of carbapenem-resistant bacteria carrying plasmids represents a potential risk due to the possible spread of resistance genes via horizontal gene transfer across the environment and hospital settings. This highly recommends the implementation of regular surveillance to monitor the spread of antimicrobial resistance among environmental bacteria, which consequently leads to its spread within communities and thus poses a great threat to human health.202540492734
184160.9997Plasmid-Determined Colistin Resistance in the North African Countries: A Systematic Review. We have conducted a systematic review to update available information on plasmid-mediated colistin resistance (mobilized colistin resistance [mcr]) genes in North African countries. We have searched the articles of PubMed, Scopus, and Web of Science databases reporting plasmid-mediated colistin resistance bacteria isolated in North African countries. After searching and selection, 30 studies that included 208 mcr-positive isolates were included. Different mcr-positive strains frequencies were recorded and ranged from 2% in clinical isolates to 12.3% in environmental samples. Escherichia coli was the predominant species recorded and these microorganisms showed high resistance to ciprofloxacin and cotrimoxazole. IncHI2 plasmids are probably the key vectors responsible for the dissemination of mcr genes in these countries. This review highlighted that the mcr-positive isolates are circulating in different ecological niches with different frequencies. Therefore, actions should be implemented to prevent the dissemination of the mcr genes within and outside of these countries, such as microbiological and molecular surveillance programs and restriction use of colistin in farming.202132522081
191970.9997Combining Functional Genomics and Whole-Genome Sequencing to Detect Antibiotic Resistance Genes in Bacterial Strains Co-Occurring Simultaneously in a Brazilian Hospital. (1) Background: The rise of multi-antibiotic resistant bacteria represents an emergent threat to human health. Here, we investigate antibiotic resistance mechanisms in bacteria of several species isolated from an intensive care unit in Brazil. (2) Methods: We used whole-genome analysis to identify antibiotic resistance genes (ARGs) and plasmids in 34 strains of Gram-negative and Gram-positive bacteria, providing the first genomic description of Morganella morganii and Ralstonia mannitolilytica clinical isolates from South America. (3) Results: We identified a high abundance of beta-lactamase genes in resistant organisms, including seven extended-spectrum beta-lactamases (OXA-1, OXA-10, CTX-M-1, KPC, TEM, HYDRO, BLP) shared between organisms from different species. Additionally, we identified several ARG-carrying plasmids indicating the potential for a fast transmission of resistance mechanism between bacterial strains. Furthermore, we uncovered two pairs of (near) identical plasmids exhibiting multi-drug resistance. Finally, since many highly resistant strains carry several different ARGs, we used functional genomics to investigate which of them were indeed functional. In this sense, for three bacterial strains (Escherichia coli, Klebsiella pneumoniae, and M. morganii), we identified six beta-lactamase genes out of 15 predicted in silico as those mainly responsible for the resistance mechanisms observed, corroborating the existence of redundant resistance mechanisms in these organisms. (4) Conclusions: Systematic studies similar to the one presented here should help to prevent outbreaks of novel multidrug-resistant bacteria in healthcare facilities.202133920372
183880.9997An overview of carbapenem-resistant organisms from food-producing animals, seafood, aquaculture, companion animals, and wildlife. Carbapenem resistance (CR) is a major global health concern. CR is a growing challenge in clinical settings due to its rapid dissemination and low treatment options. The characterization of its molecular mechanisms and epidemiology are highly studied. Nevertheless, little is known about the spread of CR in food-producing animals, seafood, aquaculture, wildlife, their environment, or the health risks associated with CR in humans. In this review, we discuss the detection of carbapenem-resistant organisms and their mechanisms of action in pigs, cattle, poultry, seafood products, companion animals, and wildlife. We also pointed out the One Health approach as a strategy to attempt the emergency and dispersion of carbapenem-resistance in this sector and to determine the role of carbapenem-producing bacteria in animals among human public health risk. A higher occurrence of carbapenem enzymes in poultry and swine has been previously reported. Studies related to poultry have highlighted P. mirabilis, E. coli, and K. pneumoniae as NDM-5- and NDM-1-producing bacteria, which lead to carbapenem resistance. OXA-181, IMP-27, and VIM-1 have also been detected in pigs. Carbapenem resistance is rare in cattle. However, OXA- and NDM-producing bacteria, mainly E. coli and A. baumannii, are cattle's leading causes of carbapenem resistance. A high prevalence of carbapenem enzymes has been reported in wildlife and companion animals, suggesting their role in the cross-species transmission of carbapenem-resistant genes. Antibiotic-resistant organisms in aquatic environments should be considered because they may act as reservoirs for carbapenem-resistant genes. It is urgent to implement the One Health approach worldwide to make an effort to contain the dissemination of carbapenem resistance.202337397005
184090.9997Extended-Spectrum β-Lactamases (ESBL) Producing Bacteria in Animals. Animals have been identified as potential reservoirs and vectors of resistance genes, with studies showing that Gram-negative bacteria can acquire resistance through the horizontal transmission of resistance genes on plasmids. It is important to understand the distribution of antimicrobial-resistant bacteria and their drug-resistant genes in animals. Previous review articles mostly focused on a single bacterium or a single animal. Our objective is to compile all ESBL-producing bacteria isolated from various animals in recent years and provide a comprehensive viewpoint. Using a thorough PubMed literature search spanning from 1 January 2020 to 30 June 2022, studies exploring extended-spectrum beta-lactamase (ESBL) producing bacteria in animals were included. ESBL-producing bacteria are present in animals from various countries around the world. The most common sources of these bacteria were farm animals, and the most frequently isolated bacteria were Escherichia coli and Klebsiella pneumoniae. The most detected ESBL genes were bla(TEM), bla(SHV), and bla(CTX-M). The presence of ESBL-producing bacteria in animals highlights the importance of the One Health approach to address the issue of antibiotic resistance. Further research is needed to better understand the epidemiology and mechanisms of the spread of ESBL-producing bacteria in animal populations and their potential impact on human and animal health.202337107023
1825100.9997Free online genome analyses reveal multiple strains in the beginning of a hospital outbreak of Enterobacter hormaechei carrying bla (OXA-436) carbapenemase gene. Free online tools for bacterial genome analyses are available for local infection surveillance at hospitals. The tools do not require bioinformatic expertise and provide rapid actionable results. Within half a year carbapenemase producing Enterobacter cloacae was reported in clinical samples from three patients who had been hospitalized at the same ward. The aim of this outbreak investigation was to characterize and compare genomes of the isolated bacteria in order to determine molecular evidence of hospital transmission. The three isolates and two isolates reported as susceptible to carbapenems were locally analyzed by whole genome sequencing (WGS). Draft genome assembly, species identification, phylogenetic analyses, typing, resistance gene determination, and plasmid analyses were carried out using free online tools from the Center for Genomic Epidemiology (CGE). Genome analyses identified all three suspected outbreak isolates as E. hormaechei carrying bla (OXA-436) gene. Two of the suspected outbreak isolates were closely related, while one was substantially different from them. Horizontal transfer of plasmid may have taken place in the ward. Detailed knowledge on the genomic composition of bacteria in suspected hospital outbreaks can be obtained by free online tools and may reveal transfer of resistance genes between different strains in addition to dissemination of specific clones.202236003132
1837110.9997Dissemination of carbapenemases producing Gram negative bacteria in the Middle East. The emergence and spread of carbapenemase-producing bacteria, that hydolyze most β-lactams, including carbapenems, are a major concern of public health system worldwide, particularly in the Middle East area. Since the plasmids harboring resistance genes could be spread across other bacterial populations, detection of carbapenemase-producing organisms has become more problematic. These organisms produce different types of enzymes including the most prevalent types including KPC, VIM, IMP, NDM, and OXA-48. Carbapenemase producers are mostly identified among Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. This study reviewed almost all papers, which conducted in the Middle East. In order to decrease the spread of resistance, the regional cooperation has been emphasized by the Middle East countries. The highest resistance, which is mediated by KPC has been observed in Afghanistan, Saudi Arabia and Jordan followed by NDM in Pakistan and OXA in Turkey and Pakistan. It is important to mention that the spread of these types have been reported sporadically in the other countries of this area. This review described the widespread carbapenemases in the Middle East area, which have been identified in an alarming rate.201526719779
1920120.9997Exploring the resistome, virulome, and mobilome of multidrug-resistant Klebsiella pneumoniae isolates: deciphering the molecular basis of carbapenem resistance. BACKGROUND: Klebsiella pneumoniae, a notorious pathogen for causing nosocomial infections has become a major cause of neonatal septicemia, leading to high morbidity and mortality worldwide. This opportunistic bacterium has become highly resistant to antibiotics due to the widespread acquisition of genes encoding a variety of enzymes such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases. We collected Klebsiella pneumoniae isolates from a local tertiary care hospital from February 2019-February 2021. To gain molecular insight into the resistome, virulome, and genetic environment of significant genes of multidrug-resistant K. pneumoniae isolates, we performed the short-read whole-genome sequencing of 10 K. pneumoniae isolates recovered from adult patients, neonates, and hospital tap water samples. RESULTS: The draft genomes of the isolates varied in size, ranging from 5.48 to 5.96 Mbp suggesting the genome plasticity of this pathogen. Various genes conferring resistance to different classes of antibiotics e.g., aminoglycosides, quinolones, sulfonamides, tetracycline, and trimethoprim were identified in all sequenced isolates. The highest resistance was observed towards carbapenems, which has been putatively linked to the presence of both class B and class D carbapenemases, bla(NDM,) and bla(OXA), respectively. Moreover, the biocide resistance gene qacEdelta1 was found in 6/10 of the sequenced strains. The sequenced isolates exhibited a broad range of sequence types and capsular types. The significant antibiotic resistance genes (ARGs) were bracketed by a variety of mobile genetic elements (MGEs). Various spontaneous mutations in genes other than the acquired antibiotic-resistance genes were observed, which play an indirect role in making these bugs resistant to antibiotics. Loss or deficiency of outer membrane porins, combined with ESBL production, played a significant role in carbapenem resistance in our sequenced isolates. Phylogenetic analysis revealed that the study isolates exhibited evolutionary relationships with strains from China, India, and the USA suggesting a shared evolutionary history and potential dissemination of similar genes amongst the isolates of different origins. CONCLUSIONS: This study provides valuable insight into the presence of multiple mechanisms of carbapenem resistance in K. pneumoniae strains including the acquisition of multiple antibiotic-resistance genes through mobile genetic elements. Identification of rich mobilome yielded insightful information regarding the crucial role of insertion sequences, transposons, and integrons in shaping the genome of bacteria for the transmission of various resistance-associated genes. Multi-drug resistant isolates that had the fewest resistance genes exhibited a significant number of mutations. K. pneumoniae isolate from water source displayed comparable antibiotic resistance determinants to clinical isolates and the highest number of virulence-associated genes suggesting the possible interplay of ARGs amongst bacteria from different sources.202438664636
1839130.9997Environmental mediation of colistin resistance in the African context. A systematic scoping review. OBJECTIVES: The prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria is a major global health concern. Resistance to last-resort antibiotics like colistin is particularly alarming. This study reviews how environmental factors have contributed to colistin resistance in the African context, where reports of colistin-resistant Gram-negative organisms are emerging. METHODS: A systematic review was conducted using multiple databases to identify articles on environmental mediation of colistin resistance in Africa. Search terms included "environment," "colistin," "mobile colistin resistance gene," and related keywords. Articles from 2015 to 2021 focusing on Africa were included. Data on country, genes detected, methods used, and bacterial species were extracted. RESULTS: Out of 847 articles identified, 26 were included in the final review. Studies were predominantly from Tunisia, Algeria, South Africa, Egypt, Nigeria, and Congo. The mobile colistin resistance (mcr-1) gene was the most common genetic variant detected. Escherichia coli (E. coli) was the predominant organism spreading mcr genes. Colistin-resistant genes were found in humans, animals, and environmental samples including manure, soil, water bodies, and wildlife. CONCLUSIONS: This review confirms the rapid spread of plasmid-mediated colistin-resistant genes in humans, animals, and the environment across Africa. The movement of resistant genes between these reservoirs is alarming. There is a need for more research into colistin resistance mechanisms and implementation of continent-wide antibiotic stewardship programs to address this emerging threat in Africa. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.202539681218
2536140.9997Global Burden of Colistin-Resistant Bacteria: Mobilized Colistin Resistance Genes Study (1980-2018). Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of mcr genes, their reservoirs and the potential pathways for human transmission are required to implement control and prevention strategies, yet such data are lacking. Publications from four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases published between 18 November 2015 and 30 December 2018 were identified. In this systematic review and meta-analysis, the prevalence of mcr genes in bacteria isolated from humans, animals, the environment and food products were investigated. A total of 974 publications were identified. 202 observational studies were included in the systematic review and 71 in the meta-analysis. mcr genes were reported from 47 countries across six continents and the overall average prevalence was 4.7% (0.1-9.3%). China reported the highest number of mcr-positive strains. Pathogenic Escherichia coli (54%), isolated from animals (52%) and harboring an IncI2 plasmid (34%) were the bacteria with highest prevalence of mcr genes. The estimated prevalence of mcr-1 pathogenic E. coli was higher in food-animals than in humans and food products, which suggests a role for foodborne transmission. This study provides a comprehensive assessment of prevalence of the mcr gene by source, organism, genotype and type of plasmid.201931623244
1573150.9997Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae, United States 2016. Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. PATIENT: The isolate harbored four known beta-lactamase genes, including plasmid-mediated bla(NDM-1) and bla(CMY-6), as well as chromosomal bla(CTX-M-15) and bla(SHV-28), which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. PATIENT: Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.201829615503
1835160.9997Insights into Acinetobacter baumannii AMA205's Unprecedented Antibiotic Resistance. The rise of antibiotic-resistant bacteria in clinical settings has become a significant global concern. Among these bacteria, Acinetobacter baumannii stands out due to its remarkable ability to acquire resistance genes and persist in hospital environments, leading to some of the most challenging infections. Horizontal gene transfer (HGT) plays a crucial role in the evolution of this pathogen. The A. baumannii AMA205 strain, belonging to sequence type ST79, was isolated from a COVID-19 patient in Argentina in 2021. This strain's antimicrobial resistance profile is notable as it harbors multiple resistance genes, some of which had not been previously described in this species. The AmpC family β-lactamase bla(CMY-6), commonly found in Enterobacterales, had never been detected in A. baumannii before. Furthermore, this is the first ST79 strain known to carry the carbapenemase bla(NDM-1) gene. Other acquired resistance genes include the carbapenemase bla(OXA-23), further complicating treatment. Susceptibility testing revealed high resistance to most antibiotic families, including cefiderocol, with significant contributions from bla(CMY-6) and bla(NDM-1) genes to the cephalosporin and carbapenem resistance profiles. The A. baumannii AMA205 genome also contains genetic traits coding for 111 potential virulence factors, such as the iron-uptake system and biofilm-associated proteins. This study underscores A. baumannii's ability to acquire multiple resistance genes and highlights the need for alternative therapies and effective antimicrobial stewardship to control the spread of these highly resistant strains.202439518977
1845170.9997Plasmid-mediated colistin resistance in Latin America and Caribbean: A systematic review. A systematic review was performed in order to integrate and synthesize available information on mcr genes dissemination in Latin America. Four databases were searched for articles reporting plasmid-mediated colistin resistance between bacteria isolated from countries of Latin America and the Caribbean. Abstract books of scientific events realized in each region were also examined. After search and selection, 48 studies that included 18,705 isolates recovered between 2000 and 2018 were evaluated. The overall frequency of mcr genes in Latin America was 2.9% (550/18,705), with IncX4 plasmids shown to be the key vectors responsible for the dissemination of genes within the continent. Brazil, Bolivia and Argentina were the countries with the highest number of mcr-positive isolates, and only Colombia (mcr-5) and Brazil (mcr-3) presented mcr genes other than type 1. Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovar Typhimurium were mainly found to carry the gene within the continent and these microorganisms showed high susceptibility to ertapenem, meropenem, piperacillin/tazobactam, fosfomycin and tigecycline. This review showed that the mcr gene is circulating in several countries of Latin America. Thus, it is important to encourage microbiological and molecular surveillance programs to avoid the spread of these genes within and outside the continent.201931336179
1918180.9997Molecular Detection of Class 1 Integron-Associated Gene Cassettes in KPC-2-Producing Klebsiella pneumoniae Clones by Whole-Genome Sequencing. The dissemination of antimicrobial resistance genes and the bacterium that harbor them have increasingly become a public concern, especially in low- and middle-income countries. The present study used whole-genome sequencing to analyze 10 KPC-2-producing Klebsiella pneumoniae isolates obtained from clinical specimens originated from Brazilian hospitals. The study documents a relevant "snapshot" of the presence of class 1 integrons in 90% of the strains presenting different gene cassettes (dfrA30, dfrA15, dfrA12, dfrA14, aadA1, aadA2, and aac(6')Iq), associated or not with transposons. Two strains presented nonclassical integron (lacking the normal 3'conserved segment). In general, most strains showed a complex resistome, characterizing them as highly resistant. Integrons, a genetically stable and efficient system, confer to bacteria as highly adaptive and low cost evolution potential to bacteria, even more serious when associated with high-risk clones, indicating an urgent need for control and prevention strategies to avoid the spread of resistance determinants in Brazil. Despite this, although the class 1 integron identified in the KPC-2-producing K. pneumoniae clones is important, our findings suggest that other elements probably have a greater impact on the spread of antimicrobial resistance, since many of these important genes were not related to this cassette.201931074706
1574190.9997Plethora of Resistance Genes in Carbapenem-Resistant Gram-Negative Bacteria in Greece: No End to a Continuous Genetic Evolution. Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four K. pneumoniae ST258, seven different profiles among the eight K. pneumoniae ST11, four profiles among the six A. baumannii ST409 and two among the three K. oxytoca. This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.202235056608