Evolution of β-lactams resistance in Gram-negative bacteria in Tunisia. - Related Documents




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501701.0000Evolution 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
154710.9999The KPC type beta-lactamases: new enzymes that confer resistance to carbapenems in Gram-negative bacilli. Antimicrobial resistance due to the continuous selective pressure from widespread use of antimicrobials in humans, animals and agriculture has been a growing problem for last decades. KPC beta-lactamases hydrolyzed beta-lactams of all classes. Especially, carbapenem antibiotics are hydrolyzed more efficiency than other beta-lactam antibiotics. The KPC enzymes are found most often in Enterobacteriaceae. Recently, these enzymes have been found in isolates of Pseudomonas aeruginosa and Acinetobacter spp. The observations of blaKPC genes isolated from different species in other countries indicate that these genes from common but unknown ancestor may have been mobilized in these areas or that blaKPC-carrying bacteria may have been passively by many vectors. The emergence of carbapenem resistance in Gram-negative bacteria is worrisome because the carbapenem resistance often may be associated with resistance to many beta-lactam and non-beta-lactam antibiotics. Treatment of infections caused by KPC-producing bacteria is extremely difficult because of their multidrug resistance, which results in high mortality rates. Therapeutic options to treat infections caused by multiresistant Gram-negative bacteria producing KPC-carbapenemases could be used polymyxin B or tigecycline.200920430717
502120.9999Beta-lactamases in Enterobacteriaceae infections in children. Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.201627180312
155930.9999Resistance 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
155840.9999Resistance 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
501850.9998Multidrug-resistant Gram-negative bacteria: a product of globalization. Global trade and mobility of people has increased rapidly over the last 20 years. This has had profound consequences for the evolution and the movement of antibiotic resistance genes. There is increasing exposure of populations all around the world to resistant bacteria arising in the emerging economies. Arguably the most important development of the last two decades in the field of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group. A consequence of the very high rates of ESBL production among Enterobacteriaceae in Asian countries is that there is a substantial use of carbapenem antibiotics, resulting in the emergence of plasmid-mediated resistance to carbapenems. This article reviews the emergence and spread of multidrug-resistant Gram-negative bacteria, focuses on three particular carbapenemases--imipenem carbapenemases, Klebsiella pneumoniae carbapenemase, and New Delhi metallo-β-lactamase--and highlights the importance of control of antibiotic use.201525737092
154660.9998Bench-to-bedside review: The role of beta-lactamases in antibiotic-resistant Gram-negative infections. Multidrug resistance has been increasing among Gram-negative bacteria and is strongly associated with the production of both chromosomal- and plasmid-encoded beta-lactamases, whose number now exceeds 890. Many of the newer enzymes exhibit broad-spectrum hydrolytic activity against most classes of beta-lactams. The most important plasmid-encoded beta-lactamases include (a) AmpC cephalosporinases produced in high quantities, (b) the expanding families of extended-spectrum beta-lactamases such as the CTX-M enzymes that can hydrolyze the advanced-spectrum cephalosporins and monobactams, and (c) carbapenemases from multiple molecular classes that are responsible for resistance to almost all beta-lactams, including the carbapenems. Important plasmid-encoded carbapenemases include (a) the KPC beta-lactamases originating in Klebsiella pneumoniae isolates and now appearing worldwide in pan-resistant Gram-negative pathogens and (b) metallo-beta-lactamases that are produced in organisms with other deleterious beta-lactamases, causing resistance to all beta-lactams except aztreonam. beta-Lactamase genes encoding these enzymes are often carried on plasmids that bear additional resistance determinants for other antibiotic classes. As a result, some infections caused by Gram-negative pathogens can now be treated with only a limited number, if any, antibiotics. Because multidrug resistance in Gram-negative bacteria is observed in both nosocomial and community isolates, eradication of these resistant strains is becoming more difficult.201020594363
251370.9998Prevalence and molecular epidemiology of carbapenem-resistant Gram-negative bacilli and their resistance determinants in the Eastern Mediterranean Region over the last decade. Carbapenem resistance in Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa is increasing worldwide, which has led the World Health Organization (WHO) to list these bacteria in the critical priority pathogens group. Infections by such pathogens pose a serious threat to hospitalised patients and are associated with clinical and economic consequences. What worsens the case is the weak pipeline of available antimicrobial agents to treat such infections and the absence of new drugs. The aim of this review was to shed light on all studies tackling carbapenem resistance in Enterobacteriaceae, A. baumannii and P. aeruginosa in the Eastern Mediterranean region, with indication for each country, description of studies timeline, prevalence of carbapenem resistance, and carbapenem resistance-encoding genes detected in these countries.202133812049
501980.9998Extended-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
154890.9998Metallo-beta-lactamases of Pseudomonas aeruginosa--a novel mechanism resistance to beta-lactam antibiotics. Since about twenty years, following the introduction into therapeutic of news beta-lactam antibiotics (broad-spectrum cephalosporins, monobactams and carbapenems), a very significant number of new beta-lactamases appeared. These enzymes confer to the bacteria which put them, the means of resisting new molecules. The genetic events involved in this evolution are of two types: evolution of old enzymes by mutation and especially appearance of new genes coming for some, from bacteria of the environment. Numerous mechanisms of enzymatic resistance to the carbapenems have been described in Pseudomonas aeruginosa. The important mechanism of inactivation carbapenems is production variety of b-lactam hydrolysing enzymes associated to carbapenemases. The metallo-beta-enzymes (IMP, VIM, SPM, GIM types) are the most clinically significant carbapenemases. P. aeruginosa posses MBLs and seem to have acquired them through transmissible genetic elements (plasmids or transposons associated with integron) and can be transmission to other bacteria. They have reported worldwide but mostly from South East Asia and Europe. The enzymes, belonging to the molecular class B family, are the most worrisome of all beta-lactamases because they confer resistance to carbapenems and all the beta-lactams (with the exception of aztreonam) and usually to aminoglycosides and quinolones. The dissemination of MBLs genes is thought to be driven by regional consumption of extended--spectrum antibiotics (e.g. cephalosporins and carbapenems), and therefore care must be taken that these drugs are not used unnecessarily.200818519228
1544100.9998Resistance 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
5015110.9998beta-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
1551120.9998Mechanisms 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
5697130.9998In 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
5027140.9998Vegetables and Fruit as a Reservoir of β-Lactam and Colistin-Resistant Gram-Negative Bacteria: A Review. Antibacterial resistance is one of the 2019 World Health Organization's top ten threats to public health worldwide. Hence, the emergence of β-lactam and colistin resistance among Gram-negative bacteria has become a serious concern. The reservoirs for such bacteria are increasing not only in hospital settings but in several other sources, including vegetables and fruit. In recent years, fresh produce gained important attention due to its consumption in healthy diets combined with a low energy density. However, since fresh produce is often consumed raw, it may also be a source of foodborne disease and a reservoir for antibiotic resistant Gram-negative bacteria including those producing extended-spectrum β-lactamase, cephalosporinase and carbapenemase enzymes, as well as those harboring the plasmid-mediated colistin resistance (mcr) gene. This review aims to provide an overview of the currently available scientific literature on the presence of extended-spectrum β-lactamases, cephalosporinase, carbapenemase and mcr genes in Gram-negative bacteria in vegetables and fruit with a focus on the possible contamination pathways in fresh produce.202134946136
2509150.9998Trends in antimicrobial-drug resistance in Japan. Multidrug resistance in gram-positive bacteria has become common worldwide. In Japan until recently, gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Serratia marcescens were controlled by carbapenems, fluoroquinolones, and aminoglycosides. However, several of these microorganisms have recently developed resistance against many antimicrobial drugs.200011076714
5020160.9998Detection of expanded-spectrum β-lactamases in Gram-negative bacteria in the 21st century. Emerging β-lactamase-producing-bacteria (ESBL, AmpC and carbapenemases) have become a serious problem in our community due to their startling spread worldwide and their ability to cause infections which are difficult to treat. Diagnosis of these β-lactamases is of clinical and epidemiological interest. Over the past 10 years, several methods have been developed aiming to rapidly detect these emerging enzymes, thus preventing their rapid spread. In this review, we describe the range of screening and detection methods (phenotypic, molecular and other) for detecting these β-lactamases but also whole genome sequencing as a tool for detecting the genes encoding these enzymes.201526162631
1572170.9998Phenotypic 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
1554180.9998Genetic 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
1848190.9998Highly Colistin-resistant Aeromonas jandaei from a Human Blood Sample. Aeromonas species are Gram-negative rods known to cause infections such as gastroenteritis, bacteremia and wound infections. Colistin is one of few treatments for multidrug-resistant Gram-negative bacteria. However, colistin-resistant bacteria carrying the mobilized colistin resistance (mcr) gene are a threat in healthcare settings worldwide. In recent years, colistin-resistant Aeromonas species have been detected in environmental and clinical samples. We analyzed the genomic characteristics of one highly colistin-resistant A. jandaei isolated from a blood sample in Nepal, which harbored four novel mcr-like genes on its chromosome. Our study strongly suggests that A. jandaei is a reservoir of colistin-resistant genes. Inappropriate use of drugs in medicine and food production should be reduced and continued global surveillance for colistin-resistant bacteria is necessary.202338855938