Genetic evolution and clinical impact in extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. - Related Documents




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155401.0000Genetic evolution and clinical impact in extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. The emergence of extended-spectrum β-lactamase (ESBL)-producing bacteria, particularly Escherichia coli and Klebsiella pneumoniae, is now a critical concern for the development of therapies against bacterial infection. ESBLs consist of three major genetic groups: TEM, SHV, and CTX-M types. Nosocomial infections due to TEM and SHV-producing K. pneumoniae strains were frequently documented until the late 1990s. The number of reports on community-acquired infections caused by CTX-M-producing E. coli strains have dramatically increased over the last decade; however, K. pneumoniae strains, of either the TEM or SHV types, are persistent and important ESBL producers. The spread of ESBL genes is associated with various mobile genetic elements, such as transposons, insertion sequences, and integrons. The rapid dissemination of ESBL genes of the CTX-M type may be related to highly complicated genetic structures. These structures harboring ESBL genes and mobile elements are found in a variety of plasmids, which often carry many other antibiotic resistance genes. Multidrug-resistant CTX-M-15-producing E. coli strains disseminate worldwide. Efficient mobile elements and plasmids may have accelerated the genetic diversity and the rapid spread of ESBL genes, and their genetic evolution has caused an emerging threat to the bacteria for which few effective drugs have been identified.201121689785
155310.9999Current epidemiology, genetic evolution and clinical impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. The worldwide spread of extended-spectrum β-lactamase (ESBL)-producing bacteria, particularly Escherichia coli and Klebsiella pneumoniae, is a critical concern for the development of therapies against multidrug-resistant bacteria. Since the 2000s, detection rates of CTX-M types ESBL-producing E. coli in the community have been high, possibly contributing to their nosocomial detection. Various factors, such as environmental sources, food animals, and international travel, accelerate the global ESBL spread in the community. The dramatic dissemination of ESBLs in the community is associated with the relatively recent emergence of CTX-M-15-producing ST131 E. coli clones, which often carry many other antibiotic resistance genes (including quinolone). The usefulness of β-lactam/β-lactamase inhibitor, particularly, piperacillin/tazobactam, has been considered as a carbapenem-sparing regimen for ESBL infections, although the global trend of AmpC β-lactamase-producing bacteria should be monitored carefully. Careful therapeutic selection and continued surveillance for the detection of multidrug-resistant bacteria are required.201829626676
155920.9999Resistance in gram-negative bacteria: enterobacteriaceae. The emergence and spread of resistance in Enterobacteriaceae are complicating the treatment of serious nosocomial infections and threatening to create species resistant to all currently available agents. Approximately 20% of Klebsiella pneumoniae infections and 31% of Enterobacter spp infections in intensive care units in the United States now involve strains not susceptible to third-generation cephalosporins. Such resistance in K pneumoniae to third-generation cephalosporins is typically caused by the acquisition of plasmids containing genes that encode for extended-spectrum beta-lactamases (ESBLs), and these plasmids often carry other resistance genes as well. ESBL-producing K pneumoniae and Escherichia coli are now relatively common in healthcare settings and often exhibit multidrug resistance. ESBL-producing Enterobacteriaceae have now emerged in the community as well. Salmonella and other Enterobacteriaceae that cause gastroenteritis may also be ESBL producers, which is of relevance when children require treatment for invasive infections. Resistance of Enterobacter spp to third-generation cephalosporins is most typically caused by overproduction of AmpC beta-lactamases, and treatment with third-generation cephalosporins may select for AmpC-overproducing mutants. Some Enterobacter cloacae strains are now ESBL and AmpC producers, conferring resistance to both third- and fourth-generation cephalosporins. Quinolone resistance in Enterobacteriaceae is usually the result of chromosomal mutations leading to alterations in target enzymes or drug accumulation. More recently, however, plasmid-mediated quinolone resistance has been reported in K pneumoniae and E coli, associated with acquisition of the qnr gene. The vast majority of Enterobacteriaceae, including ESBL producers, remain susceptible to carbapenems, and these agents are considered preferred empiric therapy for serious Enterobacteriaceae infections. Carbapenem resistance, although rare, appears to be increasing. Particularly troublesome is the emergence of KPC-type carbapenemases in New York City. Better antibiotic stewardship and infection control are needed to prevent further spread of ESBLs and other forms of resistance in Enterobacteriaceae throughout the world.200616735147
155830.9999Resistance in gram-negative bacteria: Enterobacteriaceae. The emergence and spread of resistance in Enterobacteriaceae are complicating the treatment of serious nosocomial infections and threatening to create species resistant to all currently available agents. Approximately 20% of Klebsiella pneumoniae infections and 31% of Enterobacter spp infections in intensive care units in the United States now involve strains not susceptible to third-generation cephalosporins. Such resistance in K pneumoniae to third-generation cephalosporins is typically caused by the acquisition of plasmids containing genes that encode for extended-spectrum beta-lactamases (ESBLs), and these plasmids often carry other resistance genes as well. ESBL-producing K pneumoniae and Escherichia coli are now relatively common in healthcare settings and often exhibit multidrug resistance. ESBL-producing Enterobacteriaceae have now emerged in the community as well. Salmonella and other Enterobacteriaceae that cause gastroenteritis may also be ESBL producers, which is of relevance when children require treatment for invasive infections. Resistance of Enterobacter spp to third-generation cephalosporins is most typically caused by overproduction of AmpC beta-lactamases, and treatment with third-generation cephalosporins may select for AmpC-overproducing mutants. Some Enterobacter cloacae strains are now ESBL and AmpC producers, conferring resistance to both third- and fourth-generation cephalosporins. Quinolone resistance in Enterobacteriaceae is usually the result of chromosomal mutations leading to alterations in target enzymes or drug accumulation. More recently, however, plasmid-mediated quinolone resistance has been reported in K pneumoniae and E coli, associated with acquisition of the qnr gene. The vast majority of Enterobacteriaceae, including ESBL producers, remain susceptible to carbapenems, and these agents are considered preferred empiric therapy for serious Enterobacteriaceae infections. Carbapenem resistance, although rare, appears to be increasing. Particularly troublesome is the emergence of KPC-type carbapenemases in New York City. Better antibiotic stewardship and infection control are needed to prevent further spread of ESBLs and other forms of resistance in Enterobacteriaceae throughout the world.200616813978
154440.9999Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens. During the past 15 years, emergence and dissemination of beta-lactam resistance in nosocomial Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii, became a serious problem worldwide. Especially the increasing resistance to 3rd and 4th generation cephalosporins and carbapenems is of particular concern. Gram-negative bacteria pursue various molecular strategies for development of resistance to these antibiotics: (a) generation of extended-spectrum beta-lactamases (ESBL) according to the original definition due to extension of the spectrum of already widely disseminated plasmid-encoded beta-lactamases by amino acid substitution; (b) acquisition of genes encoding ESBL from environmental bacteria as, for instance the CTX-M-type beta-lactamases from Kluyvera spp.; (c) high-level expression of chromosome-encoded beta-lactamase (bla) genes as bla(OXA) or bla(ampC) genes due to modifications in regulatory genes, mutations of the beta-lactamase promoter sequence as well as integration of insertion sequences containing an efficient promoter for intrinsic bla genes; (d) mobilization of bla genes by incorporation in integrons and horizontal transfer into other Gram-negative species such as the transfer of the ampC gene from Citrobacter freundii to Klebsiella spp.; (e) dissemination of plasmid-mediated carbapenemases as KPC and metallo-beta-lactamases, e.g. VIM and IMP; (f) non-expression of porin genes and/or efflux pump-based antibiotic resistance. This mini-review summarizes the historical emergence of beta-lactam resistance and beta-lactamases as major resistance mechanism in enteric bacteria, and also highlights recent developments such as multidrug- and carbapenem resistance.201020537585
155150.9999Mechanisms of Resistance in Gram-Negative Urinary Pathogens: From Country-Specific Molecular Insights to Global Clinical Relevance. Urinary tract infections (UTIs) are the most frequent hospital infections and among the most commonly observed community acquired infections. Alongside their clinical importance, they are notorious because the pathogens that cause them are prone to acquiring various resistance determinants, including extended-spectrum beta-lactamases (ESBL); plasmid-encoded AmpC β-lactamases (p-AmpC); carbapenemases belonging to class A, B, and D; qnr genes encoding reduced susceptibility to fluoroquinolones; as well as genes encoding enzymes that hydrolyse aminoglycosides. In Escherichia coli and Klebsiella pneumoniae, the dominant resistance mechanisms are ESBLs belonging to the CTX-M, TEM, and SHV families; p-AmpC; and (more recently) carbapenemases belonging to classes A, B, and D. Urinary Pseudomonas aeruginosa isolates harbour metallo-beta-lactamases (MBLs) and ESBLs belonging to PER and GES families, while carbapenemases of class D are found in urinary Acinetobacter baumannii isolates. The identification of resistance mechanisms in routine diagnostic practice is primarily based on phenotypic tests for the detection of beta-lactamases, such as the double-disk synergy test or Hodge test, while polymerase chain reaction (PCR) for the detection of resistance genes is mostly pursued in reference laboratories for research purposes. As the emergence of drug-resistant bacterial strains poses serious challenges in the management of UTIs, this review aimed to appraise mechanisms of resistance in relevant Gram-negative urinary pathogens, to provide a detailed map of resistance determinants in Croatia and the world, and to discuss the implications of these resistance traits on diagnostic approaches. We summarized a sundry of different resistance mechanisms among urinary isolates and showed how their prevalence highly depends on the local epidemiological context, highlighting the need for tailored interventions in the field of antimicrobial stewardship.202133925181
184760.9999Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from Humans, Animals and Food. Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical "last resort" antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli, and Enterobacter, which are major nosocomial pathogens affecting debilitated and immunocompromised patients), carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance-namely KPC (Klebsiella pneumoniae carbapenemase) (class A), IMP (imipenemase), NDM (New Delhi metallo-β-lactamase), VIM (Verona integron-encoded metallo-β-lactamase) (class B), and OXA-48 (oxacillinase, class D)-have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids), together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these "last resort" antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria.201829642473
157270.9999Phenotypic and Genomic Characterization of AmpC-Producing Klebsiella pneumoniae From Korea. The prevalence of multidrug-resistant gram-negative bacteria has continuously increased over the past few years; bacterial strains producing AmpC β-lactamases and/or extended-spectrum β-lactamases (ESBLs) are of particular concern. We combined high-resolution whole genome sequencing and phenotypic data to elucidate the mechanisms of resistance to cephamycin and β-lactamase in Korean Klebsiella pneumoniae strains, in which no AmpC-encoding genes were detected by PCR. We identified several genes that alone or in combination can potentially explain the resistance phenotype. We showed that different mechanisms could explain the resistance phenotype, emphasizing the limitations of the PCR and the importance of distinguishing closely-related gene variants.201829611388
184080.9999Extended-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
157590.9999Widespread transfer of resistance genes between bacterial species in an intensive care unit: implications for hospital epidemiology. A transferable plasmid encoding SHV-12 extended-spectrum beta-lactamase, TEM-116, and aminoglycoside resistance was responsible for two sequential clonal outbreaks of Enterobacter cloacae and Acinetobacter baumannii bacteria. A similar plasmid was present among isolates of four different bacterial species. Recognition of plasmid transfer is crucial for control of outbreaks of multidrug-resistant nosocomial pathogens.200516145160
1901100.9998Discerning the dissemination mechanisms of antibiotic resistance genes through whole genome sequencing of extended-spectrum beta-lactamase (ESBL)-producing E. coli isolated from veterinary clinics and farms in South Korea. Extended-spectrum beta-lactamase (ESBL)-producing bacteria are resistant to most beta-lactams, including third-generation cephalosporins, limiting the treatment methods against the infections they cause. In this study, we performed whole genome sequencing of ESBL-producing E. coli to determine the mechanisms underlying the dissemination of antibiotic resistance genes. We analyzed 141 ESBL-producing isolates which had been collected from 16 veterinary clinics and 16 farms in South Korea. Long- and short-read sequencing platforms were used to obtain high-quality assemblies. The results showed that bla(CTX-M) is the dominant ESBL gene type found in South Korea. The spread of bla(CTX-M) appears to have been facilitated by both clonal spread between different host species and conjugation. Most bla(CTX-M) genes were found associated with diverse mobile genetic elements that may contribute to the chromosomal integration of the genes. Diverse incompatibility groups of bla(CTX-M)-harboring plasmids were also observed, which allows their spread among a variety of bacteria. Comprehensive whole genome sequence analysis was useful for the identification of the most prevalent types of ESBL genes and their dissemination mechanisms. The results of this study suggest that the propagation of ESBL genes can occur through clonal spread and plasmid-mediated dissemination, and that suitable action plans should be developed to prevent further propagation of these genes.202438554973
1552110.9998Evolution of β-Lactam Antibiotic Resistance in Proteus Species: From Extended-Spectrum and Plasmid-Mediated AmpC β-Lactamases to Carbapenemases. The management of infectious diseases has proven to be a daunting task for clinicians worldwide, and the rapid development of antibiotic resistance among Gram-negative bacteria is making it even more challenging. The first-line therapy is empirical, and it most often comprises β-lactam antibiotics. Among Gram-negative bacteria, Proteus mirabilis, an important community and hospital pathogen associated primarily with urinary tract and wound infection, holds a special place. This review's aim was to collate and examine recent studies investigating β-lactam resistance phenotypes and mechanisms of Proteus species and the global significance of its β-lactam resistance evolution. Moreover, the genetic background of resistance traits and the role of mobile genetic elements in the dissemination of resistance genes were evaluated. P. mirabilis as the dominant pathogen develops resistance to expanded-spectrum cephalosporins (ESC) by producing extended-spectrum β-lactamases (ESBL) and plasmid-mediated AmpC β-lactamases (p-AmpC). β-lactamase-mediated resistance to carbapenems in Enterobacterales, including Proteus spp., is mostly due to expression of carbapenemases of class A (KPC); class B (metallo-β-lactamases or MBLs of IMP, VIM, or NDM series); or class D or carbapenem-hydrolyzing oxacillinases (CHDL). Previously, a dominant ESBL type in P. mirabilis was TEM-52; yet, lately, it has been replaced by CTX-M variants, particularly CTX-M-14. ESC resistance can also be mediated by p-AmpC, with CMY-16 as the dominant variant. Carbapenem resistance in Proteus spp. is a challenge due to its intrinsic resistance to colistin and tigecyclin. The first carbapenemases reported belonged to class B, most frequently VIM-1 and NDM-5. In Europe, predominantly France and Belgium, a clonal lineage positive for OXA-23 CHDL spreads rapidly undetected, due to its low-level resistance to carbapenems. The amazing capacity of Proteus spp. to accumulate a plethora of various resistance traits is leading to multidrug or extensively drug-resistant phenotypes.202540142401
1557120.9998Carbapenemase-producing Klebsiella pneumoniae. The continuing emergence of infections due to multidrug resistant bacteria is a serious public health problem. Klebsiella pneumoniae, which commonly acquires resistance encoded on mobile genetic elements, including ones that encode carbapenemases, is a prime example. K. pneumoniae carrying such genetic material, including both blaKPC and genes encoding metallo-β-lactamases, have spread globally. Many carbapenemase-producing K. pneumoniae are resistant to multiple antibiotic classes beyond β-lactams, including tetracyclines, aminoglycosides, and fluoroquinolones. The optimal treatment, if any, for infections due to these organisms is unclear but, paradoxically, appears to often require the inclusion of an optimally administered carbapenem.201425343037
1842130.9998Emergence of mcr-9.1 in Extended-Spectrum-β-Lactamase-Producing Clinical Enterobacteriaceae in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome. Extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analyzed to determine their resistomes, mobilomes, and evolutionary relationships to global strains. The global phylogenomics of mcr genes and mcr-9.1-bearing genomes were further analyzed. Ten isolates were ESBL positive. The isolates were multidrug resistant and phylogenetically related to global clones but distant from local strains. Multiple resistance genes, including bla (CTX-M-15) bla (TEM-1), and mcr-9.1, were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed bla (CTX-M-15) and bla (TEM-1) Common plasmid types included IncF, IncH, and ColRNAI. mcr-9 was of close sequence identity to mcr-3, mcr-5, mcr-7, mcr-8, and mcr-10. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A to F), with those of this study belonging to clade B. Enterobacter species and Salmonella species are the main hosts of mcr-9.1 globally, although diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying, due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices.IMPORTANCE Colistin is currently the last-resort antibiotic for difficult-to-treat bacterial infections. However, colistin resistance genes that can move from bacteria to bacteria have emerged, threatening the safe treatment of many bacterial infections. One of these genes, mcr-9.1, has emerged in South Africa in bacteria that are multidrug resistant, further limiting treatment options for clinicians. In this work, we show that this new gene is disseminating worldwide through Enterobacter and Salmonella species through multiple plasmids. This worrying observation requires urgent action to prevent further escalation of this gene in South Africa and Africa.202032430406
1902140.9998Large-scale analysis of putative plasmids in clinical multidrug-resistant Escherichia coli isolates from Vietnamese patients. INTRODUCTION: In the past decades, extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Escherichia coli isolates have been detected in Vietnamese hospitals. The transfer of antimicrobial resistance (AMR) genes carried on plasmids is mainly responsible for the emergence of multidrug-resistant E. coli strains and the spread of AMR genes through horizontal gene transfer. Therefore, it is important to thoroughly study the characteristics of AMR gene-harboring plasmids in clinical multidrug-resistant bacterial isolates. METHODS: The profiles of plasmid assemblies were determined by analyzing previously published whole-genome sequencing data of 751 multidrug-resistant E. coli isolates from Vietnamese hospitals in order to identify the risk of AMR gene horizontal transfer and dissemination. RESULTS: The number of putative plasmids in isolates was independent of the sequencing coverage. These putative plasmids originated from various bacterial species, but mostly from the Escherichia genus, particularly E. coli species. Many different AMR genes were detected in plasmid contigs of the studied isolates, and their number was higher in CR isolates than in ESBL-producing isolates. Similarly, the bla(KPC-2), bla(NDM-5), bla(OXA-1), bla(OXA-48), and bla(OXA-181) β-lactamase genes, associated with resistance to carbapenems, were more frequent in CR strains. Sequence similarity network and genome annotation analyses revealed high conservation of the β-lactamase gene clusters in plasmid contigs that carried the same AMR genes. DISCUSSION: Our study provides evidence of horizontal gene transfer in multidrug-resistant E. coli isolates via conjugative plasmids, thus rapidly accelerating the emergence of resistant bacteria. Besides reducing antibiotic misuse, prevention of plasmid transmission also is essential to limit antibiotic resistance.202337323902
5019150.9998Extended-spectrum beta-lactamases: definition, history, an update on their genetic environment and detection methods. Bacterial resistance remains a major challenge in the therapeutic field. Beta-lactam antibiotics are widely used to treat Enterobacteriaceae, especially third-generation cephalosporins (3GCs), which are used in infections caused by bacteria resistant to first- and second-line antibiotics. However, these bacteria have been able to develop resistance against the used antibiotics through the production of extended-spectrum beta-lactamase (ESBL) enzymes. These enzymes inactivate 3GCs and are sensitive to beta-lactamase inhibitors such as clavulanic acid. This resistance is acquired by plasmids (IncF, IncI, IncK…) which carry mobile genetic elements (insertion sequence, transposon…) with genes coding for these enzymes, namely, the bla (CTX-M), bla (SHV) and bla (TEM), which code for the most frequent types of ESBL (CTX-M, SHV and TEM). Unfortunately, when ESBLs are not identified in time, appropriate treatment is delayed, reducing the chances of cure. Current data highlight the spread and dangerousness of ESBL-producing bacteria worldwide and confirm the priority given to these bacteria by the World Health Organization, which insists on vigilance in identifying them, both in patients and through surveillance studies. The aim of the current review is to provide a better understanding of ESBLs, to highlight their historical evolution and to show the importance of their genetic environment in the dissemination and spread of these enzymes worldwide, as well as the techniques used to detect them in laboratory studies. Current data demonstrate the degree of danger posed by ESBL-producing bacteria and confirm the priority given to these bacteria by the World Health Organization for the development of new antimicrobial agents.202540554694
5015160.9998beta-Lactam resistance and beta-lactamases in bacteria of animal origin. beta-Lactams are among the most clinically important antimicrobials in both human and veterinary medicine. Bacterial resistance to beta-lactams has been increasingly observed in bacteria, including those of animal origin. The mechanisms of beta-lactam resistance include inaccessibility of the drugs to their target, target alterations and/or inactivation of the drugs by beta-lactamases. The latter contributes predominantly to beta-lactam resistance in Gram-negative bacteria. A variety of beta-lactamases have been identified in bacteria derived from food-producing and companion animals and may further serve as a reservoir for beta-lactamase-producing bacteria in humans. While this review mainly describes beta-lactamases from animal-derived Escherichia coli and Salmonella spp., beta-lactamases from animal-derived Campylobacter spp., Enterococcus spp., Staphylococcus spp. and other pathogens are also discussed. Of particular concern are the increasingly-isolated plasmid-encoded AmpC-type CMY and extended-spectrum CTX-M beta-lactamases, which mediate acquired resistance to extended-spectrum beta-lactams. The genes encoding these enzymes often coexist with other antimicrobial resistance determinants and can also be associated with transposons/integrons, increasing the potential enrichment of multidrug resistant bacteria by multiple antimicrobial agents as well as dissemination of the resistance determinants among bacterial species. Characterization of beta-lactam-resistant animal-derived bacteria warrants further investigation of the type and distribution of beta-lactamases in bacteria of animal origin and their potential impact on human medicine.200717306475
5017170.9998Evolution of β-lactams resistance in Gram-negative bacteria in Tunisia. Antimicrobial resistance is a major health problem worldwide, but marked variations in the resistance profiles of bacterial pathogens are found between countries and in different patient settings. In Tunisia, the strikingly high prevalence of resistance of bacteria to penicillins and cephalorosporins drugs including fourth generation in clinical isolates of Gram negative bacteria has been reported. During 30 years, the emerging problem of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates is substantial, and some unique enzymes have been found. Recently, evidence that Gram-negative bacteria are resistant to nearly all available antimicrobial agents, including carbapenems, have emerged.201121438848
1849180.9998Carbapenemase-Producing Elizabethkingia Meningoseptica from Healthy Pigs Associated with Colistin Use in Spain. Carbapenems are considered last-resort antimicrobials, especially for treating infections involving multidrug-resistant Gram-negative bacteria. In recent years, extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Gram-negative bacteria have become widespread in hospitals, community settings, and the environment, reducing the range of effective therapeutic alternatives. The use of colistin to treat infection caused by these multi-drug bacteria may favour the selection and persistence of carbapenem-resistant bacteria. In this study, it is described, for the first time to our knowledge, a carbapenemase-producing isolate of Elizabethkingia meningoseptica from healthy pigs in Spain. The isolate we report was recovered during a study to detect colistin-resistant bacteria from faecal samples of healthy food-production animals using a chromogenic selective medium. Unexpectedly, we found an isolate of Elizabethkingia meningoseptica with high Minimum Inhibitory Concentration (MIC) values for several antibiotics tested. Molecular analysis did not show any mcr family genes related with colistin resistance, but two carbapenemase genes, bla(B-12_1) and bla(GOB-17_1), were detected. This finding in healthy animals could suggest that colistin may favour the selection and persistence of carbapenem-resistant bacteria.201931514353
5697190.9998In Silico Analysis of Extended-Spectrum β-Lactamases in Bacteria. The growing bacterial resistance to available β-lactam antibiotics is a very serious public health problem, especially due to the production of a wide range of β-lactamases. At present, clinically important bacteria are increasingly acquiring new elements of resistance to carbapenems and polymyxins, including extended-spectrum β-lactamases (ESBLs), carbapenemases and phosphoethanolamine transferases of the MCR type. These bacterial enzymes limit therapeutic options in human and veterinary medicine. It must be emphasized that there is a real risk of losing the ability to treat serious and life-threatening infections. The present study aimed to design specific oligonucleotides for rapid PCR detection of ESBL-encoding genes and in silico analysis of selected ESBL enzymes. A total of 58 primers were designed to detect 49 types of different ESBL genes. After comparing the amino acid sequences of ESBLs (CTX-M, SHV and TEM), phylogenetic trees were created based on the presence of conserved amino acids and homologous motifs. This study indicates that the proposed primers should be able to specifically detect more than 99.8% of all described ESBL enzymes. The results suggest that the in silico tested primers could be used for PCR to detect the presence of ESBL genes in various bacteria, as well as to monitor their spread.202134356733