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  1 / 15366 MEDLINE  
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[PMID]:29472192
[Au] Autor:Powers JH; Evans SR; Kesselheim AS
[Ad] Endereço:George Washington University School of Medicine, Washington, DC, USA.
[Ti] Título:Studying new antibiotics for multidrug resistant infections: are today's patients paying for unproved future benefits?
[So] Source:BMJ;360:k587, 2018 02 22.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Infecções Bacterianas/tratamento farmacológico
Farmacorresistência Bacteriana Múltipla
[Mh] Termos MeSH secundário: Aprovação de Drogas
Previsões
Seres Humanos
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180224
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k587


  2 / 15366 MEDLINE  
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[PMID]:29373935
[Au] Autor:Falcone M; Viale P; Tiseo G; Pai M
[Ad] Endereço:a Department of Public Health and Infectious Diseases , "Sapienza" University of Rome , Rome , Italy.
[Ti] Título:Pharmacokinetic drug evaluation of avibactam + ceftazidime for the treatment of hospital-acquired pneumonia.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):331-340, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a combination of a third-generation cephalosporin and a non-ß-lactam, ß-lactamase inhibitor, recently approved for urinary tract infections and complicated abdominal infections. Moreover, it represents a treatment option for patients with hospital acquired pneumonia (HAP), especially when caused by multidrug-resistant (MDR) bacteria. Areas covered: The review focuses on the pharmacokinetics (PK) of CAZ-AVI in HAP and on preclinical and clinical studies evaluating PK/pharmacodynamics (PD) in this field. Expert opinion: In vitro and in vivo data about PK/PD of CAZ-AVI confirm that penetration of CAZ-AVI in the epithelial lining fluid (ELF) represents approximately 30% of the plasma concentrations. Clinical studies documented that CAZ-AVI 2000 mg/500 mg every 8 h is the optimal dose regimen to achieve the PK/PD target attainment in patients with HAP. Thus, CAZ-AVI could represent an option both to treat HAP caused by Gram-negative bacilli (GNB) displaying resistance to most of the antibiotics and to reduce the use of carbapenems, limiting the onset of resistance profiles among GNB. Additional information about specific patients populations, such as critically-ill subjects or pediatric patients, are needed for a more individualized use of CAZ-AVI.
[Mh] Termos MeSH primário: Antibacterianos/administração & dosagem
Compostos Azabicíclicos/administração & dosagem
Ceftazidima/administração & dosagem
Pneumonia Bacteriana/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibacterianos/farmacocinética
Compostos Azabicíclicos/farmacocinética
Ceftazidima/farmacocinética
Infecção Hospitalar/tratamento farmacológico
Infecção Hospitalar/microbiologia
Relação Dose-Resposta a Droga
Farmacorresistência Bacteriana Múltipla
Seres Humanos
Pneumonia Bacteriana/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Azabicyclo Compounds); 0 (avibactam, ceftazidime drug combination); 9M416Z9QNR (Ceftazidime)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180128
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1434142


  3 / 15366 MEDLINE  
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[PMID]:29458540
[Au] Autor:Li Y; Zhang L; Zhou Y; Zhang Z; Zhang X
[Ad] Endereço:1​Department of Immunology, College of Preclinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan, PR China.
[Ti] Título:Survival of bactericidal antibiotic treatment by tolerant persister cells of Klebsiella pneumoniae.
[So] Source:J Med Microbiol;67(3):273-281, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Persister cells, a subpopulation of tolerant cells within the bacterial culture, are commonly thought to be responsible for antibiotic therapy failure and infection recurrence. Klebsiella pneumoniae is a notorious human pathogen for its increasing resistance to antibiotics and wide involvement in severe infections. In this study, we aimed to investigate the persister subpopulation of K. pneumoniae. METHODOLOGY: The presence of persisters in K. pneumoniae was determined by treatment with high concentrations of antibiotics, used alone or in combination. The effect of low level of antibiotics on persister formation was investigated by pre-exposure of cells to antibiotics with low concentrations followed by higher doses. The dependence of persister levels on growth phase was determined by measuring the survival ability of cells along the growth stages upon exposure to a high concentration of antibiotic. Analysis on persister type was carried out by persister elimination assays.Results/Key findings. We show that K. pneumoniae produces high levels of tolerant persister cells to survive treatment by a variety of high concentrations of bactericidal antibiotics and persister formation is prevalent among K. pneumoniae clinical strains. Besides, we find that persister cells can be induced by low concentrations of antibiotics. Finally, we provide evidence that persister formation is growth phase-dependent and Type II persisters dominate the persister subpopulation during the entire exponential phase of K. pneumoniae. CONCLUSION: Our study describes the formation of tolerant persister cells that allow survival of treatment by high concentrations of antibiotics in K. pneumoniae.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Klebsiella pneumoniae/efeitos dos fármacos
Klebsiella pneumoniae/fisiologia
Viabilidade Microbiana/efeitos dos fármacos
[Mh] Termos MeSH secundário: Contagem de Colônia Microbiana
Farmacorresistência Bacteriana Múltipla
Tolerância a Medicamentos
Seres Humanos
Infecções por Klebsiella/microbiologia
Klebsiella pneumoniae/crescimento & desenvolvimento
Testes de Sensibilidade Microbiana
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000680


  4 / 15366 MEDLINE  
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[PMID]:29342216
[Au] Autor:Narayanaswamy VP; Giatpaiboon SA; Uhrig J; Orwin P; Wiesmann W; Baker SM; Townsend SM
[Ad] Endereço:Synedgen, Inc., Claremont, California, United States of America.
[Ti] Título:In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus.
[So] Source:PLoS One;13(1):e0191522, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The incidence of multidrug-resistant (MDR) organisms, including methicillin-resistant Staphylococcus aureus (MRSA), is a serious threat to public health. Progress in developing new therapeutics is being outpaced by antibiotic resistance development, and alternative agents that rapidly permeabilize bacteria hold tremendous potential for treating MDR infections. A new class of glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG) is under development as an alternative to traditional antibiotic strategies to treat MRSA infections. This study demonstrates the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU) in ≤ 12-hours at doses that are non-toxic to mammalian cells. PAAG also sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by the observed reduction in the oxacillin MIC to below the antibiotic resistance breakpoint. The effect of PAAG and standard antibiotics including vancomycin, oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies showed that S. aureus developed resistance to PAAG at a rate slower than to mupirocin but similar to bacitracin. PAAG was observed to resensitize drug-resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage resistance study, reducing MICs of mupirocin and bacitracin below their clinical sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Glucosamina/análogos & derivados
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Polímeros/farmacologia
Polissacarídeos/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/química
Farmacorresistência Bacteriana Múltipla
Glucosamina/química
Glucosamina/farmacologia
Glicosídeos
Seres Humanos
Técnicas In Vitro
Resistência a Meticilina
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação
Staphylococcus aureus Resistente à Meticilina/metabolismo
Testes de Sensibilidade Microbiana
Mupirocina/farmacologia
Permeabilidade/efeitos dos fármacos
Polímeros/química
Polissacarídeos/química
Propídio/farmacocinética
Infecções Estafilocócicas/tratamento farmacológico
Infecções Estafilocócicas/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycosides); 0 (Polymers); 0 (Polysaccharides); 0 (pinocembrin 7-O-apiosyl(1-5)apiosyl(1-2)glucopyranoside); 0 (poly-N (acetyl, arginyl)glucosamine); 36015-30-2 (Propidium); D0GX863OA5 (Mupirocin); N08U5BOQ1K (Glucosamine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191522


  5 / 15366 MEDLINE  
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[PMID]:29390257
[Au] Autor:Pérez Heras I; Sanchez-Gomez JC; Beneyto-Martin P; Ruano-de-Pablo L; Losada-Pinedo B
[Ti] Título:Community-onset extended-spectrum ß-lactamase producing Escherichia coli in urinary tract infections in children from 2015 to 2016: Prevalence, risk factors, and resistances.
[So] Source:Medicine (Baltimore);96(50):e8571, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Over the past 10 years, the resistances among microbes are increasing gradually in Europe and greater resistances are seen in southern countries. We studied the prevalence of community-onset ESBL-producing Escherichia coli urinary tract infections in children.As secondary objectives, we analyzed associated risk factors and the resistance patterns in ESBL-producing E coli isolates.Retrospective observational study in a tertiary care hospital about children ≤14 years old with community-onset E coli urinary tract infection. The variables studied were age, sex, ESBL-producing, antibiotic therapy 7 to 30 days before the infection, hospitalization 7 to 30 days before the infection, nefrourologic pathology, and vesicoureteral reflux.Between January 1st, 2015 and December 31st, 2016, 229 isolates of E coli were obtained, of whom 21 (9.2%) where ESBL-producing E coli. Median age in non-ESBL-producing was 18 months versus 7 months in ESBL-producing group. Fourteen (66%) of the ESBL-producing group were men (P = .001), 5 (23.8%) were hospitalized 30 days before the infection (P = .001), 12 (57.1%) had nefrourological pathology (P = .003), 6 (28.5%) had vesicoureteral reflux (P = .032). Previous antibiotic therapy was not statistically significant. Multiple regression analyses between sex and 30 days previous hospitalization were r = 3.51 (P = .0001). Multidrug resistant isolates among ESBL-producing E coli was 12 (57%).The retrospective study allowed assessing the problem of ESBL-producing isolates in the outpatient settings. Some risk factors from past studies were confirmed and a combined risk is suggested. The resistant spectrum should be taken into account when choosing antibiotic regimens.
[Mh] Termos MeSH primário: Farmacorresistência Bacteriana Múltipla
Infecções por Escherichia coli/tratamento farmacológico
Infecções por Escherichia coli/epidemiologia
Infecções Urinárias/microbiologia
[Mh] Termos MeSH secundário: Fatores Etários
Antibacterianos/uso terapêutico
Infecções Comunitárias Adquiridas/epidemiologia
Escherichia coli
Feminino
Hospitalização
Seres Humanos
Lactente
Masculino
Prevalência
Estudos Retrospectivos
Fatores de Risco
Espanha/epidemiologia
Infecções Urinárias/tratamento farmacológico
Infecções Urinárias/epidemiologia
Refluxo Vesicoureteral/epidemiologia
beta-Lactamases
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); EC 3.5.2.6 (beta-Lactamases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008571


  6 / 15366 MEDLINE  
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[PMID]:29373597
[Au] Autor:Ciesinski L; Guenther S; Pieper R; Kalisch M; Bednorz C; Wieler LH
[Ad] Endereço:Centre for Infection Medicine, Institute of Microbiology and Epizootics, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
[Ti] Título:High dietary zinc feeding promotes persistence of multi-resistant E. coli in the swine gut.
[So] Source:PLoS One;13(1):e0191660, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High levels of zinc oxide are used frequently as feed additive in pigs to improve gut health and growth performance and are still suggested as an alternative to antimicrobial growth promoters. However, we have recently described an increase of multi-resistant E. coli in association to zinc feeding in piglets. This previous study focused on clonal diversity of E. coli, observing the effect on multi-resistant strains by chance. To shed further light into this highly important topic and falsify our previous findings, we performed a zinc pig feeding trial where we specifically focused on in-depth analysis of antimicrobial resistant E. coli. Under controlled experimental conditions, piglets were randomly allocated to a high dietary zinc (zinc group) and a background zinc feeding group (control group). At different ages samples were taken from feces, digesta, and mucosa and absolute E. coli numbers were determined. A total of 2665 E. coli isolates were than phenotypically tested for antimicrobial resistance and results were confirmed by minimum inhibitory concentration testing for random samples. In piglets fed with high dietary zinc, we detected a substantial increase of multi-resistant E. coli in all gut habitats tested, ranging from 28.9-30.2% multi-resistant E. coli compared to 5.8-14.0% in the control group. This increase was independent of the total number of E. coli. Interestingly, the total amount of the E. coli population decreased over time. Thus, the increase of the multi-resistant E. coli populations seems to be linked with persistence of the resistant population, caused by the influence of high dietary zinc feeding. In conclusion, these findings corroborate our previous report linking high dietary zinc feeding of piglets with the occurrence of antimicrobial resistant E. coli and therefore question the feeding of high dietary zinc oxide as alternative to antimicrobial growth promoters.
[Mh] Termos MeSH primário: Ração Animal
Dieta
Escherichia coli/fisiologia
Intestinos/microbiologia
Zinco/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Farmacorresistência Bacteriana Múltipla
Escherichia coli/efeitos dos fármacos
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191660


  7 / 15366 MEDLINE  
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[PMID]:29317622
[Au] Autor:Zwama M; Yamasaki S; Nakashima R; Sakurai K; Nishino K; Yamaguchi A
[Ad] Endereço:Laboratory of Cell Membrane Structural Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, 567-0047, Japan.
[Ti] Título:Multiple entry pathways within the efflux transporter AcrB contribute to multidrug recognition.
[So] Source:Nat Commun;9(1):124, 2018 01 09.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AcrB is the major multidrug exporter in Escherichia coli. Although several substrate-entrances have been identified, the specificity of these various transport paths remains unclear. Here we present evidence for a substrate channel (channel 3)  from the central cavity of the AcrB trimer, which is connected directly to the deep pocket without first passing the switch-loop and the proximal pocket . Planar aromatic cations, such as ethidium, prefer channel 3 to channels 1 and 2. The efflux through channel 3 increases by targeted mutations and is not in competition with the export of drugs such as minocycline and erythromycin through channels 1 and 2. A switch-loop mutant, in which the pathway from the proximal to the deep pocket is hindered, can export only channel 3-utilizing drugs. The usage of multiple entrances thus contributes to the recognition and transport of a wide range of drugs with different physicochemical properties.
[Mh] Termos MeSH primário: Farmacorresistência Bacteriana Múltipla/genética
Proteínas de Escherichia coli/genética
Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética
Transdução de Sinais/genética
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Escherichia coli/efeitos dos fármacos
Escherichia coli/genética
Escherichia coli/metabolismo
Proteínas de Escherichia coli/química
Proteínas de Escherichia coli/metabolismo
Etídio/química
Etídio/metabolismo
Testes de Sensibilidade Microbiana
Modelos Moleculares
Proteínas Associadas à Resistência a Múltiplos Medicamentos/química
Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
Mutação
Domínios Proteicos
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AcrB protein, E coli); 0 (Anti-Bacterial Agents); 0 (Escherichia coli Proteins); 0 (Multidrug Resistance-Associated Proteins); EN464416SI (Ethidium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02493-1


  8 / 15366 MEDLINE  
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[PMID]:29318906
[Au] Autor:Choi JJ; McCarthy MW
[Ad] Endereço:a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
[Ti] Título:Cefiderocol: a novel siderophore cephalosporin.
[So] Source:Expert Opin Investig Drugs;27(2):193-197, 2018 Feb.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The emergence of multidrug-resistant bacterial pathogens has led to a global public health emergency and novel therapeutic options and drug-delivery systems are urgently needed. Cefiderocol is a siderophore cephalosporin antibiotic that has recently been developed to combat a variety of bacterial pathogens, including ß-lactam- and carbapenem-resistant organisms. Areas covered: This paper provides an overview of the mutational and plasmid-mediated mechanisms of ß-lactam and carbapenem resistance, the biochemical pathways of siderophores in bacterial iron metabolism, and how cefiderocol may be able to provide better targeted antimicrobial therapy that escape these drug-resistant mechanisms. We also explore the pharmacokinetics of this new compound as well as results from preclinical and clinical studies. Expert opinion: There is an urgent need for novel antimicrobial agents to address the emergence of multidrug-resistant pathogens, which are an increasing cause of morbidity and mortality worldwide. Our understanding of multidrug-resistance and bacterial biochemical pathways continues to expand, and the development of cefiderocol specifically targeting siderophore-mediated iron transport shows potential in escaping mechanisms of drug resistance. Cefiderocol, which demonstrates a favorable side effect profile, has the potential to become first-line therapy for our most aggressive and lethal multidrug-resistant Gram-negative pathogens.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Cefalosporinas/farmacologia
Infecções por Bactérias Gram-Negativas/tratamento farmacológico
[Mh] Termos MeSH secundário: Antibacterianos/administração & dosagem
Antibacterianos/efeitos adversos
Cefalosporinas/administração & dosagem
Cefalosporinas/efeitos adversos
Sistemas de Liberação de Medicamentos
Desenho de Drogas
Farmacorresistência Bacteriana Múltipla
Bactérias Gram-Negativas/efeitos dos fármacos
Infecções por Bactérias Gram-Negativas/microbiologia
Seres Humanos
Sideróforos/administração & dosagem
Sideróforos/efeitos adversos
Sideróforos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (Siderophores); 0 (cefiderocol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2018.1426745


  9 / 15366 MEDLINE  
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[PMID]:28456705
[Au] Autor:Li QJ; Jiao WW; Yin QQ; Li YJ; Li JQ; Xu F; Sun L; Xiao J; Qi H; Wang T; Mokrousov I; Huang HR; Shen AD
[Ad] Endereço:Ministry of Education Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics (Capital Medical University), National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute
[Ti] Título:Positive epistasis of major low-cost drug resistance mutations rpoB531-TTG and katG315-ACC depends on the phylogenetic background of Mycobacterium tuberculosis strains.
[So] Source:Int J Antimicrob Agents;49(6):757-762, 2017 Jun.
[Is] ISSN:1872-7913
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mycobacterium tuberculosis Beijing genotype strains increasingly circulate in different world regions, either as historical endemic, e.g. in East Asia, or recently imported, e.g. in South America, and this family is regarded as the most successful lineage of the global tuberculosis (TB) epidemic. Here we analysed the transmission capacity of these strains in the context of their phylogenetic background and drug resistance mutations. The study collection included all multidrug resistant (MDR) strains of Beijing genotype isolated in Beijing Chest Hospital, the largest tertiary TB facility in North China, in 2011-2013 (n = 278). Strains were subjected to NTF/IS6110 and 24-loci MIRU-VNTR analysis. Drug resistance mutations were detected in rpoB, katG, inhA and oxyR-ahpC. A total of 58 and 220 strains were assigned to the ancient and modern Beijing sublineages, respectively. 24-MIRU-VNTR clustering was higher in modern versus ancient Beijing strains (35.9% vs. 12.1%; P <0.001). After taking into consideration the presence of rpoB and katG mutations, clustering decreased to 15.9% in modern and 0% in ancient strains. The most frequent combination of mutations (rpoB531-TTG and katG315-ACC) was more prevalent in clustered versus non-clustered isolates in the modern sublineage (23/35 vs. 47/185; P <0.0001). To conclude, a combination of the known low-fitness-cost rpoB531-TTG and katG315-ACC mutations likely facilitates the increased transmission ability of MDR strains of the modern but not ancient Beijing sublineage. Accordingly, positive epistasis of major low-cost drug resistance-conferring mutations is influenced by the phylogenetic background of M. tuberculosis strains.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Farmacorresistência Bacteriana Múltipla
Mutação
Mycobacterium tuberculosis/classificação
Mycobacterium tuberculosis/efeitos dos fármacos
Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
Tuberculose Resistente a Múltiplos Medicamentos/transmissão
[Mh] Termos MeSH secundário: Adulto
Idoso
China/epidemiologia
Análise por Conglomerados
Transmissão de Doença Infecciosa
Feminino
Seres Humanos
Masculino
Meia-Idade
Epidemiologia Molecular
Mycobacterium tuberculosis/genética
Mycobacterium tuberculosis/isolamento & purificação
Filogenia
Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:29334931
[Au] Autor:Dzotam JK; Simo IK; Bitchagno G; Celik I; Sandjo LP; Tane P; Kuete V
[Ad] Endereço:Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
[Ti] Título:In vitro antibacterial and antibiotic modifying activity of crude extract, fractions and 3',4',7-trihydroxyflavone from Myristica fragrans Houtt against MDR Gram-negative enteric bacteria.
[So] Source:BMC Complement Altern Med;18(1):15, 2018 Jan 15.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nutmeg is the seed kernel inside the fruit of Myristica fragrans Houtt. (Myristicaceae). It possesses various pharmacological activities but is used in Cameroon only for its flavor in making cakes. The present study thus aimed to investigate the in vitro antibacterial activity and antibiotic modifying activities of crude seed kernel methanol extract (MFS), fractions (MFSa-e) as well as 3',4',7-trihydroxyflavone from Myristica fragrans against a panel of multi-drug resistant (MDR) Gram-negative bacteria. METHODS: The modified rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay was used to determine the Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) on the tested bacteria, as well as those of antibiotics in association with the extract and/or isolated compound. Column chromatography was used for the fractionation and purification of the seed kernel extract whilst the chemical structures of compounds were determined using spectroscopic techniques. RESULTS: Phytochemical investigations lead to the isolation of 3',4',7-trihydroxyflavone from the fraction MFSb. The crude extract showed antibacterial activity with MICs ranging from 32 to 1024 µg/mL on the majority of the 29 tested Gram-negative bacterial strains. Fraction MFSb inhibited the growth of 100% (29/29) of the tested bacterial strains, as well as the compound 3',4',7-trihydroxyflavone (12/12) with a MIC values ranging from 32 to 1024 µg/mL, and 4 to 128 µg/mL respectively. The lowest MIC value (4 µg/mL) was recorded with 3',4',7-trihydroxyflavone against Providencia stuartii ATCC299645 as well as the best MBC value (16 µg/mL) against the same strain. In the presence of Phenylalanine-Arginine-ß-Naphthylamide (PAßN), an efflux pumps inhibitor, the activity of the extract increased on 73.33% (11/15) meanwhile that of 3',4',7-trihydroxyflavone increased on 100% tested bacteria. The compound 3',4',7-trihydroxyflavone potentiated the activity of antibiotics in the majority of the tested bacterial strains. CONCLUSION: The results of the present work provide additional information on the use of nutmeg and it major antibacterial component, 3',4',7-trihydroxyflavone, as a potential drug in the treatment of bacterial infections including multidrug resistant phenotypes.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Flavonoides/farmacologia
Bactérias Gram-Negativas/efeitos dos fármacos
Myristica fragrans/química
Extratos Vegetais/farmacologia
[Mh] Termos MeSH secundário: Camarões
Cloranfenicol/farmacologia
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos
Testes de Sensibilidade Microbiana
Sementes/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3',4',7-trihydroxyflavone); 0 (Anti-Bacterial Agents); 0 (Flavonoids); 0 (Plant Extracts); 66974FR9Q1 (Chloramphenicol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-018-2084-1



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