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  1 / 32226 MEDLINE  
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[PMID]:29484749
[Au] Autor:Khosravi AD; Meghdadi H; Ghadiri AA; Alami A; Sina AH; Mirsaeidi M
[Ad] Endereço:Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
[Ti] Título:rpoB gene mutations among Mycobacterium tuberculosis isolates from extrapulmonary sites.
[So] Source:APMIS;126(3):241-247, 2018 Mar.
[Is] ISSN:1600-0463
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to analyze mutations occurring in the rpoB gene of Mycobacterium tuberculosis (MTB) isolates from clinical samples of extrapulmonary tuberculosis (EPTB). Seventy formalin-fixed, paraffin-embedded samples and fresh tissue samples from confirmed EPTB cases were analyzed. Nested PCR based on the rpoB gene was performed on the extracted DNAs, combined with cloning and subsequent sequencing. Sixty-seven (95.7%) samples were positive for nester PCR. Sequence analysis of the 81 bp region of the rpoB gene demonstrated mutations in 41 (61.2%) of 67 sequenced samples. Several point mutations including deletion mutations at codons 510, 512, 513 and 515, with 45% and 51% of the mutations in codons 512 and 513 respectively were seen, along with 26% replacement mutations at codons 509, 513, 514, 518, 520, 524 and 531. The most common alteration was Gln → His, at codon 513, presented in 30 (75.6%) isolates. This study demonstrated sequence alterations in codon 513 of the 81 bp region of the rpoB gene as the most common mutation occurred in 75.6% of molecularly confirmed rifampin-resistant strains. In addition, simultaneous mutation at codons 512 and 513 was demonstrated in 34.3% of the isolates.
[Mh] Termos MeSH primário: Antibióticos Antituberculose/farmacologia
Proteínas de Bactérias/genética
RNA Polimerases Dirigidas por DNA/genética
Farmacorresistência Bacteriana/genética
Mycobacterium tuberculosis/genética
Rifampina/farmacologia
Tuberculose/microbiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Células Cultivadas
Feminino
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana
Meia-Idade
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/isolamento & purificação
Mutação Puntual/genética
Deleção de Sequência/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antitubercular); 0 (Bacterial Proteins); 0 (rpoB protein, Mycobacterium tuberculosis); EC 2.7.7.6 (DNA-Directed RNA Polymerases); VJT6J7R4TR (Rifampin)
[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:180228
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12804


  2 / 32226 MEDLINE  
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[PMID]:29377957
[Au] Autor:Yang D; Chen L; Chen Z
[Ad] Endereço:Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.
[Ti] Título:The timing of azithromycin treatment is not associated with the clinical prognosis of childhood Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.
[So] Source:PLoS One;13(1):e0191951, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Mycoplasma pneumoniae infection is a major cause of community-acquired pneumonia in children. We performed a retrospective study to evaluate the clinical impact of the timing of azithromycin treatment in children with Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings. METHODS AND FINDINGS: A total of 623 patients were enrolled in this study and were divided into 2 groups according to the timing of azithromycin therapy. Children who received azithromycin within 3 days (72 hours) after the onset of Mycoplasma pneumoniae pneumonia were classified into the early azithromycin treatment group (n = 174), whereas the late azithromycin treatment group (n = 449) comprised children treated with azithromycin more than 72 hours after symptom onset. We evaluated clinical prognosis according to demographic, clinical and laboratory characteristics. Although the early azithromycin treatment group exhibited a longer fever duration after azithromycin administration (7.17±4.12 versus 4.82±3.99 days, P<0.01), the total fever duration exhibited no significant difference (9.02±4.58 versus 9.57±4.91 days, P = 0.212). After azithromycin therapy, the two groups exhibited no significant differences with respect to improvements in the laboratory and radiological findings (all P>0.05). CONCLUSION: The timing of azithromycin treatment is not associated with the clinical prognosis of Mycoplasma pneumoniae pneumonia in children in high macrolide-resistant Mycoplasma pneumoniae prevalence settings.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Azitromicina/uso terapêutico
Macrolídeos/uso terapêutico
Pneumonia Bacteriana/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Farmacorresistência Bacteriana
Feminino
Seres Humanos
Lactente
Masculino
Pneumonia Bacteriana/patologia
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Macrolides); 83905-01-5 (Azithromycin)
[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:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191951


  3 / 32226 MEDLINE  
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[PMID]:29338017
[Au] Autor:Graham RMA; Hiley L; Rathnayake IU; Jennison AV
[Ad] Endereço:Public Health Microbiology, Forensic and Scientific Services, Queensland Department of Health, Coopers Plains, Queensland, Australia.
[Ti] Título:Comparative genomics identifies distinct lineages of S. Enteritidis from Queensland, Australia.
[So] Source:PLoS One;13(1):e0191042, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Salmonella enterica is a major cause of gastroenteritis and foodborne illness in Australia where notification rates in the state of Queensland are the highest in the country. S. Enteritidis is among the five most common serotypes reported in Queensland and it is a priority for epidemiological surveillance due to concerns regarding its emergence in Australia. Using whole genome sequencing, we have analysed the genomic epidemiology of 217 S. Enteritidis isolates from Queensland, and observed that they fall into three distinct clades, which we have differentiated as Clades A, B and C. Phage types and MLST sequence types differed between the clades and comparative genomic analysis has shown that each has a unique profile of prophage and genomic islands. Several of the phage regions present in the S. Enteritidis reference strain P125109 were absent in Clades A and C, and these clades also had difference in the presence of pathogenicity islands, containing complete SPI-6 and SPI-19 regions, while P125109 does not. Antimicrobial resistance markers were found in 39 isolates, all but one of which belonged to Clade B. Phylogenetic analysis of the Queensland isolates in the context of 170 international strains showed that Queensland Clade B isolates group together with the previously identified global clade, while the other two clades are distinct and appear largely restricted to Australia. Locally sourced environmental isolates included in this analysis all belonged to Clades A and C, which is consistent with the theory that these clades are a source of locally acquired infection, while Clade B isolates are mostly travel related.
[Mh] Termos MeSH primário: Genoma Bacteriano
Salmonella enteritidis/isolamento & purificação
[Mh] Termos MeSH secundário: Farmacorresistência Bacteriana/genética
Filogenia
Polimorfismo de Nucleotídeo Único
Queensland
Salmonella enteritidis/classificação
Salmonella enteritidis/efeitos dos fármacos
Salmonella enteritidis/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[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:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191042


  4 / 32226 MEDLINE  
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[PMID]:29458676
[Au] Autor:Gorla MC; Cassiolato AP; Pinhata JMW; de Moraes C; Corso A; Gagetti P; Lemos AP
[Ad] Endereço:1​Bacteriology Department, Adolfo Lutz Institute, Av. Dr. Arnaldo 351, São Paulo, CEP 01246-902, SP, Brazil.
[Ti] Título:Emergence of resistance to ciprofloxacin in Neisseria meningitidis in Brazil.
[So] Source:J Med Microbiol;67(3):286-288, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To prevent secondary invasive meningococcal disease (IMD) cases and outbreaks, antimicrobial prophylaxis of high-risk contacts is indicated. This study reports two ciprofloxacin-resistant Neisseria meningitidis strains in Brazil. The 3523 N. meningitidis isolates collected throughout Brazil from 2009 to 2016 were evaluated for antimicrobial resistance. Meningococcal isolates showing minimal inhibitory concentrations, MICs≥0.125µg ml to ciprofloxacin, were analysed to determine the presence of mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC genes. Two ciprofloxacin-resistant N. meningitidis isolates were found, both presenting a single mutation in the quinolone resistance-determining region of the gyrA gene. These results confirmed that ciprofloxacin is still a first-line drug for chemoprophylaxis. However, we highlight the importance of continued surveillance to monitor the trends of N. meningitidis susceptibility profiles to the antimicrobials recommended for chemoprophylaxis and IMD treatment.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Ciprofloxacino/farmacologia
Farmacorresistência Bacteriana/genética
Infecções Meningocócicas/microbiologia
Neisseria meningitidis/efeitos dos fármacos
Neisseria meningitidis/genética
[Mh] Termos MeSH secundário: Brasil/epidemiologia
DNA Girase/genética
DNA Topoisomerase IV/genética
Fluoroquinolonas/farmacologia
Seres Humanos
Infecções Meningocócicas/epidemiologia
Testes de Sensibilidade Microbiana
Tipagem de Sequências Multilocus
Mutação
Neisseria gonorrhoeae/isolamento & purificação
Quinolonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Fluoroquinolones); 0 (Quinolones); 5E8K9I0O4U (Ciprofloxacin); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[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.0.000685


  5 / 32226 MEDLINE  
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[PMID]:29458674
[Au] Autor:Nair S; Poonacha N; Desai S; Hiremath D; Tuppad D; Mohan T; Chikkamadaiah R; Durgaiah M; Kumar S; Channabasappa S; Vipra A; Sharma U
[Ad] Endereço:GangaGen Biotechnologies Pvt Ltd., Bangalore, India.
[Ti] Título:Restoration of sensitivity of a diverse set of drug-resistant Staphylococcus clinical strains by bactericidal protein P128.
[So] Source:J Med Microbiol;67(3):296-307, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: P128, a phage-derived lysin, exerts antibacterial activity on staphylococci by cleaving the pentaglycine-bridge of peptidoglycan. We sought to determine whether the presence of P128 could re-sensitize drug-resistant bacteria to antibiotics by virtue of its cell wall degrading property. METHODOLOGY: P128 was tested in combination with standard-of-care (SoC) drugs by chequerboard assays on planktonic cells and biofilms of strains individually resistant to these drugs. The bactericidal effect of P128 and drug combinations on planktonic cells and biofilms was measured by c.f.u. reduction assays. A mouse model of MRSA bacteraemia was used to test the efficacy of P128 and oxacillin in combination. RESULTS: A combination of sub-MIC P128 (0.025-0.20 µg ml ) and 0.5 µg ml of oxacillin resulted in inhibition of bacterial growth in four MRSA strains. Similar results were seen with all the other drugs tested, wherein sub-MIC of P128 re-sensitized S. aureus and CoNS strains to SoC drugs. The chequerboard assays on strains of S. aureus and CoNS showed that combinations of P128 and antibiotics consistently inhibited bacterial growth on biofilms. Data from scanning electron microscopy and c.f.u. reduction assays on drug-resistant S. aureus and CoNS demonstrated that sub-MICs of P128 and SoC antibiotics could kill biofilm-embedded bacteria. In vivo, a combination of sub-therapeutic doses of P128 and oxacillin could help protect animals from fatal bacteraemia. CONCLUSION: The ability of P128 to re-sensitize bacteria to SoC drugs suggests that combinations of P128 and SoC antibiotics can potentially be developed to treat infections caused by drug-resistant strains of staphylococci.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Proteínas Recombinantes de Fusão/farmacologia
Staphylococcus aureus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Biofilmes/efeitos dos fármacos
Biofilmes/crescimento & desenvolvimento
Modelos Animais de Doenças
Seres Humanos
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Camundongos
Testes de Sensibilidade Microbiana
Oxacilina/farmacologia
Proteínas Recombinantes de Fusão/metabolismo
Infecções Estafilocócicas/microbiologia
Staphylococcus aureus/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (P128 antistaphylococcal chimeric protein); 0 (Recombinant Fusion Proteins); UH95VD7V76 (Oxacillin)
[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.0.000697


  6 / 32226 MEDLINE  
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[PMID]:29215335
[Au] Autor:Djordjevic ZM; Folic MM; Jankovic SM
[Ad] Endereço:Clinic of Control Hospital Infections, Kragujevac Centre Clinical, Kragujevac, Serbia.
[Ti] Título:Previous Antibiotic Exposure and Antimicrobial Resistance Patterns of spp. and aeruginosa Isolated from Patients with Nosocomial Infections.
[So] Source:Balkan Med J;34(6):527-533, 2017 12 01.
[Is] ISSN:2146-3131
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The alarming spread of antibiotic-resistant bacteria causing healthcare-associated infections has been extensively reported in recent medical literature. AIMS: To compare trends in antimicrobial consumption and development of resistance among isolates of spp. and that cause hospital infections. STUDY DESIGN: Cross-sectional study. METHODS: A study was conducted in a tertiary healthcare institution in central Serbia, during the 7-year period between January 2009 and December 2015. The incidence rate of infections caused by or , as well as their resistance density to commonly used antibiotics, were calculated. Utilization of antibiotics was expressed as the number of defined daily doses per 1000 patient-days. RESULTS: A statistically significant increase in resistance density in 2015 compared to the first year of observation was noted for , but not for , to third-generation cephalosporins (p=0.008), aminoglycosides (p=0.005), carbapenems (p=0.003), piperacillin/tazobactam (p=0.025), ampicillin/sulbactam (p=0.009) and tigecycline (p=0.048). CONCLUSION: Our study showed that there is an association between the resistance density of spp. and utilization of carbapenems, tigecycline and aminoglycosides. A multifaceted intervention is needed to decrease the incidence rate of and hospital infections, as well as their resistance density to available antibiotics.
[Mh] Termos MeSH primário: Infecções por Acinetobacter/microbiologia
Acinetobacter/efeitos dos fármacos
Antibacterianos/uso terapêutico
Infecção Hospitalar/tratamento farmacológico
Infecção Hospitalar/microbiologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Infecções por Pseudomonas/microbiologia
Pseudomonas aeruginosa/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acinetobacter/isolamento & purificação
Infecções por Acinetobacter/tratamento farmacológico
Adulto
Estudos Transversais
Seres Humanos
Testes de Sensibilidade Microbiana
Padrões de Prática Médica/estatística & dados numéricos
Infecções por Pseudomonas/tratamento farmacológico
Pseudomonas aeruginosa/isolamento & purificação
Sérvia/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.4274/balkanmedj.2016.1844


  7 / 32226 MEDLINE  
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[PMID]:27777243
[Au] Autor:Fleming A; Barry L; Byrne S; Prentice M
[Ad] Endereço:School of Pharmacy, University College Cork, Cork, Ireland.
[Ti] Título:Antimicrobial susceptibility of long term care facility and general practice urine samples in patients 65 years and older: an observational study.
[So] Source:Eur J Public Health;27(2):307-312, 2017 04 01.
[Is] ISSN:1464-360X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Antimicrobial resistance in long-term care facilities (LTCFs) poses a risk to elderly residents. The aim of this observational study was to investigate recent patterns of antimicrobial susceptibility in urine samples submitted to the Microbiology Laboratory at Cork University Hospital (CUH) from LTCFs in the greater Cork region. The antimicrobial susceptibilities of LTCF and General Practitioner (GP) urine samples sent to CUH, for patients aged over 65 years of age, were compared. Methods: A retrospective analysis of the antimicrobial susceptibilities of urine samples submitted to the microbiology laboratory at CUH in quarter one of 2011-2014 was conducted. LTCF and GP urine sample susceptibilities, for patients over 65 years of age, were compared using Chi square statistics. Results: Overall, the LTCF urine samples were less susceptible than GP urine samples to the antimicrobials recommended in the national urinary tract infection guidelines; trimethoprim, nitrofurantoin, cephalexin, co-amoxiclav, ciprofloxacin and amoxicillin ( P < 0.001). Important trends in antimicrobial susceptibility over the time period were noted. A significant reduction in susceptibility to co-amoxiclav was found between Q1 2011 and Q1 2014 in both settings (GP P = 0.013, LTCF P = 0.005). This study provides important information which will contribute to the revision of antimicrobial prescribing guidelines in the future. Conclusion: This study highlights the need for continuous surveillance of antimicrobial susceptibility trends in LTCFs. Antimicrobial stewardship strategies are urgently required to address antimicrobial resistance and appropriate antimicrobial prescribing in the LTCF setting.
[Mh] Termos MeSH primário: Antibacterianos/urina
Farmacorresistência Bacteriana
Medicina Geral/estatística & dados numéricos
Instituição de Longa Permanência para Idosos/estatística & dados numéricos
Casas de Saúde/estatística & dados numéricos
Infecções Urinárias/urina
[Mh] Termos MeSH secundário: Idoso
Antibacterianos/uso terapêutico
Feminino
Seres Humanos
Irlanda
Assistência de Longa Duração
Masculino
Estudos Retrospectivos
Infecções Urinárias/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1093/eurpub/ckw138


  8 / 32226 MEDLINE  
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Suffys, Philip N
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[PMID]:29367657
[Au] Autor:Benjak A; Avanzi C; Singh P; Loiseau C; Girma S; Busso P; Fontes ANB; Miyamoto Y; Namisato M; Bobosha K; Salgado CG; da Silva MB; Bouth RC; Frade MAC; Filho FB; Barreto JG; Nery JAC; Bührer-Sékula S; Lupien A; Al-Samie AR; Al-Qubati Y; Alkubati AS; Bretzel G; Vera-Cabrera L; Sakho F; Johnson CR; Kodio M; Fomba A; Sow SO; Gado M; Konaté O; Stefani MMA; Penna GO; Suffys PN; Sarno EN; Moraes MO; Rosa PS; Baptista IMFD; Spencer JS; Aseffa A; Matsuoka M; Kai M; Cole ST
[Ad] Endereço:Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland.
[Ti] Título:Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae.
[So] Source:Nat Commun;9(1):352, 2018 01 24.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.
[Mh] Termos MeSH primário: Anti-Infecciosos/farmacologia
Farmacorresistência Bacteriana/genética
Mycobacterium leprae/efeitos dos fármacos
Filogenia
[Mh] Termos MeSH secundário: Códon sem Sentido
DNA Bacteriano/química
Genoma Bacteriano
Seres Humanos
Testes de Sensibilidade Microbiana
Mycobacterium leprae/genética
Mycobacterium leprae/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Codon, Nonsense); 0 (DNA, Bacterial)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02576-z


  9 / 32226 MEDLINE  
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[PMID]:29295973
[Au] Autor:Blaskovich MAT; Hansford KA; Gong Y; Butler MS; Muldoon C; Huang JX; Ramu S; Silva AB; Cheng M; Kavanagh AM; Ziora Z; Premraj R; Lindahl F; Bradford TA; Lee JC; Karoli T; Pelingon R; Edwards DJ; Amado M; Elliott AG; Phetsang W; Daud NH; Deecke JE; Sidjabat HE; Ramaologa S; Zuegg J; Betley JR; Beevers APG; Smith RAG; Roberts JA; Paterson DL; Cooper MA
[Ad] Endereço:Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.blaskovich@uq.edu.au.
[Ti] Título:Protein-inspired antibiotics active against vancomycin- and daptomycin-resistant bacteria.
[So] Source:Nat Commun;9(1):22, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The public health threat posed by a looming 'post-antibiotic' era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast to nature's control of biological pathways via modulation of membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation of the glycopeptide antibiotic vancomycin via selective targeting of bacterial membranes. Peptide libraries based on positively charged electrostatic effector sequences are ligated to N-terminal lipophilic membrane-insertive elements and then conjugated to vancomycin. These modified lipoglycopeptides, the 'vancapticins', possess enhanced membrane affinity and activity against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria, and retain activity against glycopeptide-resistant strains. Optimised antibiotics show in vivo efficacy in multiple models of bacterial infection. This membrane-targeting strategy has potential to 'revitalise' antibiotics that have lost effectiveness against recalcitrant bacteria, or enhance the activity of other intravenous-administered drugs that target membrane-associated receptors.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Bactérias/efeitos dos fármacos
Daptomicina/farmacologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Proteínas de Membrana/metabolismo
Vancomicina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antibacterianos/metabolismo
Antibacterianos/farmacocinética
Bactérias/classificação
Sobrevivência Celular/efeitos dos fármacos
Glicopeptídeos/metabolismo
Células HEK293
Células Hep G2
Seres Humanos
Masculino
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Camundongos
Testes de Sensibilidade Microbiana
Viabilidade Microbiana/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycopeptides); 0 (Membrane Proteins); 6Q205EH1VU (Vancomycin); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02123-w


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[PMID]:29256290
[Au] Autor:Elal Mus T; Cetinkaya F; Cibik R; Soyutemiz GE; Simsek H; Coplu N
[Ad] Endereço:1 Department of Food Processing, Vocational School of Keles, University of Uludag , Bursa , Turkey.
[Ti] Título:Pathogenicity determinants and antibiotic resistance profiles of enterococci from foods of animal origin in Turkey.
[So] Source:Acta Vet Hung;65(4):461-474, 2017 12.
[Is] ISSN:0236-6290
[Cp] País de publicação:Hungary
[La] Idioma:eng
[Ab] Resumo:In this study, the presence of genes responsible for the pathogenicity and antibiotic resistance profile of enterococci isolated from various foodstuffs of animal origin was investigated. The percentage prevalence of enterococci was 54.1% (203/375) and the average count was found to be 3.81 log cfu/ml-g. Species-specific primers revealed Enterococcus faecalis as the predominant species carrying one or more virulence-associated traits of efa, gelE, ace, esp and agg genetic markers. Only one E. faecium isolate (from milk) was positive for the esp gene. Regarding antibiotic resistance, the highest frequency of resistance was observed for tetracycline (21.7%), followed by quinupristin/dalfopristin (13.3%), ciprofloxacin (2.0%), penicillin (2.0%), linezolid (1.0%), ampicillin (1.0%), streptomycin (1.0%), and gentamicin (0.5%). Enterococcus faecalis showed a higher prevalence of antibiotic resistance than other enterococci. The percentage of multidrug resistance among the isolates was 3.4%. Twenty-nine E. faecalis isolates (26.6%) carrying one of the virulence-associated traits were at the same time resistant to at least one antibiotic. Our results show that foods of animal origin, including ready-to-eat products, may be reservoirs of antibiotic-resistant and potentially virulent enterococci.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Laticínios/microbiologia
Farmacorresistência Bacteriana
Enterococcus/efeitos dos fármacos
Carne/microbiologia
[Mh] Termos MeSH secundário: Animais
Bovinos
Microbiologia de Alimentos
Testes de Sensibilidade Microbiana
Aves Domésticas
Turquia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.1556/004.2017.044



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