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[PMID]:29458684
[Au] Autor:Wise MG; Horvath E; Young K; Sahm DF; Kazmierczak KM
[Ad] Endereço:1​International Health Management Associates, Schaumburg, Illinois, USA.
[Ti] Título:Global survey of Klebsiella pneumoniae major porins from ertapenem non-susceptible isolates lacking carbapenemases.
[So] Source:J Med Microbiol;67(3):289-295, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To understand the diversity of porin disruption in Klebsiella pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36, were examined in a set of isolates that did not harbour traditional carbapenem-hydrolysing enzymes, but nevertheless tested non-susceptible to ertapenem. METHODS: A world-wide collection of Klebsiella pneumoniae isolates that were part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance project over the years 2008-2014 were characterised with regard to their ß-lactamase gene carriage and potential permeability defects. Four hundred and eighty-seven isolates that did not carry carbapenemase genes, but were non-susceptible to ertapenem, were investigated by sequence analysis of the genes encoding OmpK35 and OmpK36. Isolates without obvious genetic lesions in either major porin gene were further examined by outer membrane protein SDS-PAGE. RESULTS: The majority of isolates, 83.0 % (404/487), exhibited clear genetic disruption in either or both of the ompK35 and ompK36 genes. Among the proportion of the collection with the highest ertapenem MIC value (>4 mg l ), 60.5 % (115/190) showed mutation in both porin genes. Isolates without obvious genetic mutations were examined by SDS-PAGE, and 90.4 % (75/83) were found to lack or show altered expression of at least one of the major OMPs when compared to an ertapenem sensitive control strain. CONCLUSION: This study illustrates that porin deficiency in Klebsiella pneumoniae is a widespread phenomenon, and in combination with ESBLs and/or AmpC enzymes, likely accounts for the elevated ertapenem MICs observed in this study.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Proteínas de Bactérias/genética
Klebsiella pneumoniae/genética
Porinas/genética
beta-Lactamas/farmacologia
[Mh] Termos MeSH secundário: Proteínas de Bactérias/metabolismo
Carbapenêmicos/farmacologia
DNA Bacteriano/genética
Eletroforese em Gel de Poliacrilamida
Seres Humanos
Infecções por Klebsiella/epidemiologia
Infecções por Klebsiella/microbiologia
Klebsiella pneumoniae/efeitos dos fármacos
Klebsiella pneumoniae/isolamento & purificação
Klebsiella pneumoniae/metabolismo
Testes de Sensibilidade Microbiana
Mutação
beta-Lactamases/genética
beta-Lactamases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Carbapenems); 0 (DNA, Bacterial); 0 (OmpK35 porin, Klebsiella pneumoniae); 0 (OmpK36 protein, Klebsiella pneumoniae); 0 (Porins); 0 (beta-Lactams); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (carbapenemase); G32F6EID2H (ertapenem)
[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.0.000691


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[PMID]:29306206
[Au] Autor:Zhou P; Liang Y; Zhang H; Jiang H; Feng K; Xu P; Wang J; Wang X; Ding K; Luo C; Liu M; Wang Y
[Ad] Endereço:School of Pharmacy, Fudan University, Shanghai 201203, China; State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
[Ti] Título:Design, synthesis, biological evaluation and cocrystal structures with tubulin of chiral ß-lactam bridged combretastatin A-4 analogues as potent antitumor agents.
[So] Source:Eur J Med Chem;144:817-842, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A diverse of chiral ß-lactam bridged analogues of combretastatin A-4 (CA-4), 3-substituted 1,4-diaryl-2-azetidinones, were asymmetrically synthesized and biologically evaluated, leading to identify a number of potent anti-proliferative compounds represented by 14b and 14c with IC values of 0.001-0.021 µM, against four human cancer cell lines (A2780, Hela, SKOV-3 and MDA-MB-231). Structure-activity relationship (SAR) studies on all stereoisomers of 14b and 14c revealed that the absolute configurations of the chiral centers at 3- and 4-position were critically important for the activity and generally a trans configuration between the "A" and "B" rings is optimal. In addition, 14b and 14c displayed less cytotoxicity on normal human oviduct epithelial cells than malignant cells indicating good selectivity in vitro. Further biochemical evaluation and cocrystal structures with tubulin demonstrated that both compounds disrupted tubulin polymerization through interacting at the colchicine-binding site, suppressed angiogenesis in vitro and in vivo, blocked cell cycle progression at mitotic phase and induced cellular apoptosis. The in vivo assays verified that both compounds inhibited xenograft tumor growth in nude mice with acceptable therapeutic window, showing promising potentials for further clinical development.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Desenho de Drogas
Estilbenos/farmacologia
Moduladores de Tubulina/farmacologia
Tubulina (Proteína)/química
beta-Lactamas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Feminino
Células HeLa
Seres Humanos
Camundongos
Camundongos Endogâmicos
Camundongos Nus
Modelos Moleculares
Estrutura Molecular
Neoplasias Experimentais/tratamento farmacológico
Neoplasias Experimentais/patologia
Polimerização/efeitos dos fármacos
Estilbenos/química
Relação Estrutura-Atividade
Tubulina (Proteína)/metabolismo
Moduladores de Tubulina/síntese química
Moduladores de Tubulina/química
beta-Lactamas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Stilbenes); 0 (Tubulin); 0 (Tubulin Modulators); 0 (beta-Lactams); I5590ES2QZ (fosbretabulin)
[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:180107
[St] Status:MEDLINE


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[PMID]:28469034
[Au] Autor:Dupnik K
[Ad] Endereço:Division of Infectious Diseases, Center for Global Health, Weill Medical College of Cornell University, New York, NY 10065, USA. Email: kad9040@med.cornell.edu.
[Ti] Título:What's "hapten"-ing in ß-lactam hypersensitivity?
[So] Source:Sci Transl Med;9(388), 2017 May 03.
[Is] ISSN:1946-6242
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Piperacillin binding to proteins can but does not always induce a hypersensitivity reaction.
[Mh] Termos MeSH primário: Piperacilina/farmacologia
beta-Lactamas/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Seres Humanos
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (beta-Lactams); X00B0D5O0E (Piperacillin)
[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:170505
[St] Status:MEDLINE


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[PMID]:29254478
[Au] Autor:Zhang H; Yang Q; Liao K; Ni Y; Yu Y; Hu B; Sun Z; Huang W; Wang Y; Wu A; Feng X; Luo Y; Chu Y; Chen S; Cao B; Su J; Duan Q; Zhang S; Shao H; Kong H; Gui B; Hu Z; Badal R; Xu Y
[Ad] Endereço:Division of Microbiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.
[Ti] Título:Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.
[So] Source:BMC Infect Dis;17(1):776, 2017 12 18.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. METHODS: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. RESULTS: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively. CONCLUSIONS: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.
[Mh] Termos MeSH primário: Abdome/microbiologia
Antibacterianos/farmacologia
Infecções por Escherichia coli/microbiologia
Escherichia coli/efeitos dos fármacos
Infecções por Klebsiella/microbiologia
Klebsiella pneumoniae/efeitos dos fármacos
[Mh] Termos MeSH secundário: Cefalosporinas/farmacologia
China/epidemiologia
Infecções Comunitárias Adquiridas/epidemiologia
Infecções Comunitárias Adquiridas/microbiologia
Infecção Hospitalar/microbiologia
Escherichia coli/classificação
Escherichia coli/genética
Escherichia coli/isolamento & purificação
Infecções por Escherichia coli/epidemiologia
Seres Humanos
Imipenem/farmacologia
Incidência
Infecções Intra-Abdominais/microbiologia
Infecções por Klebsiella/epidemiologia
Klebsiella pneumoniae/classificação
Klebsiella pneumoniae/genética
Klebsiella pneumoniae/isolamento & purificação
Testes de Sensibilidade Microbiana
beta-Lactamas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (beta-Lactams); 71OTZ9ZE0A (Imipenem); G32F6EID2H (ertapenem)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2873-z


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[PMID]:29195768
[Au] Autor:Menon V; Davis R; Shackel N; Espedido BA; Beukers AG; Jensen SO; van Hal SJ
[Ad] Endereço:Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
[Ti] Título:Failure of daptomycin ß-Lactam combination therapy to prevent resistance emergence in Enterococcus faecium.
[So] Source:Diagn Microbiol Infect Dis;90(2):120-122, 2018 Feb.
[Is] ISSN:1879-0070
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Daptomycin ß-Lactam combination therapy offers "protection" against daptomycin non-susceptibility (DNS) development in Enterococcus faecium. We report failure of this strategy and the importance of source control. Mutations were detected in the LiaF and cls genes in DNS isolates. A single DNS isolate contained an unrecognized mutation, which requires confirmation.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Daptomicina/uso terapêutico
Enterococcus faecium/efeitos dos fármacos
Infecções por Bactérias Gram-Positivas/tratamento farmacológico
beta-Lactamas/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Antibacterianos/farmacologia
Daptomicina/farmacologia
Farmacorresistência Bacteriana/genética
Quimioterapia Combinada
Enterococcus faecium/genética
Infecções por Bactérias Gram-Positivas/microbiologia
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana
Mutação/genética
beta-Lactamas/farmacologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (beta-Lactams); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171203
[St] Status:MEDLINE


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[PMID]:29197733
[Au] Autor:Alborz M; Jarrahpour A; Pournejati R; Karbalaei-Heidari HR; Sinou V; Latour C; Brunel JM; Sharghi H; Aberi M; Turos E; Wojtas L
[Ad] Endereço:Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71946-84795, Iran.
[Ti] Título:Synthesis and biological evaluation of some novel diastereoselective benzothiazole ß-lactam conjugates.
[So] Source:Eur J Med Chem;143:283-291, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Highly diastereoselective synthesis of some novel benzothiazole-substituted ß-lactam hybrids was achieved starting from (benzo[d]thiazol-2-yl)phenol as an available precursor. This is the first time (benzo[d]thiazol-2-yl)phenoxyacetic acid has been used as ketene source in synthesizing monocyclic 2-azetidinones. These compounds were evaluated for their antimicrobial activities against a large panel of Gram-positive and Gram-negative bacterial strains and moderate activities were encountered. Antimalarial data revealed that adding methoxyphenyl or ethoxyphenyl group on the ß-lactam ring makes compounds that are more potent. Moreover, hemolytic activity and mammalian cell toxicity survey of the compounds showed their potential as a medicine.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Antifúngicos/farmacologia
Antimaláricos/farmacologia
Benzotiazóis/farmacologia
beta-Lactamas/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Anti-Infecciosos
Antifúngicos/síntese química
Antifúngicos/química
Antimaláricos/síntese química
Antimaláricos/química
Bactérias/efeitos dos fármacos
Bactérias/crescimento & desenvolvimento
Benzotiazóis/síntese química
Benzotiazóis/química
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Fungos/efeitos dos fármacos
Fungos/crescimento & desenvolvimento
Células Hep G2
Seres Humanos
Estrutura Molecular
Plasmodium falciparum/efeitos dos fármacos
Estereoisomerismo
Relação Estrutura-Atividade
beta-Lactamas/síntese química
beta-Lactamas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Infective Agents); 0 (Antifungal Agents); 0 (Antimalarials); 0 (Benzothiazoles); 0 (beta-Lactams); G5BW2593EP (benzothiazole)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171204
[St] Status:MEDLINE


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[PMID]:28455333
[Au] Autor:Kusada H; Tamaki H; Kamagata Y; Hanada S; Kimura N
[Ad] Endereço:Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
[Ti] Título:A Novel Quorum-Quenching -Acylhomoserine Lactone Acylase from Acidovorax sp. Strain MR-S7 Mediates Antibiotic Resistance.
[So] Source:Appl Environ Microbiol;83(13), 2017 Jul 01.
[Is] ISSN:1098-5336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:-Acylhomoserine lactone acylase (AHL acylase) is a well-known enzyme responsible for disrupting cell-cell communication (quorum sensing) in bacteria. Here, we isolated and characterized a novel and unique AHL acylase (designated MacQ) from a multidrug-resistant bacterium, sp. strain MR-S7. The purified MacQ protein heterologously expressed in degraded a wide variety of AHLs, ranging from C to C side chains with or without 3-oxo substitutions. We also observed that AHL-mediated virulence factor production in a plant pathogen, , was dramatically attenuated by coculture with MacQ-overexpressing , whereas with an empty vector was unable to quench the pathogenicity, which strongly indicates that MacQ can act as a quorum-quenching enzyme and interfere with the quorum-sensing system in the pathogen. In addition, this enzyme was found to be capable of degrading a wide spectrum of ß-lactams (penicillin G, ampicillin, amoxicillin, carbenicillin, cephalexin, and cefadroxil) by deacylation, clearly indicating that MacQ is a bifunctional enzyme that confers both quorum quenching and antibiotic resistance on strain MR-S7. MacQ has relatively low amino acid sequence identity to any of the known acylases (<39%) and has among the broadest substrate range. Our findings provide the possibility that AHL acylase genes can be an alternative source of antibiotic resistance genes posing a threat to human health if they migrate and transfer to pathogenic bacteria. -Acylhomoserine lactones (AHLs) are well-known signal molecules for bacterial cell-cell communication (quorum sensing), and AHL acylase, which is able to degrade AHLs, has been recognized as a major target for quorum-sensing interference (quorum quenching) in pathogens. In this work, we succeeded in isolating a novel AHL acylase (MacQ) from a multidrug-resistant bacterium and demonstrated that the MacQ enzyme could confer multidrug resistance as well as quorum quenching on the host organism. Indeed, the purified MacQ protein was found to be bifunctional and capable of degrading not only various AHL derivatives but also multiple ß-lactam antibiotics by deacylation activities. Although quorum quenching and antibiotic resistance have been recognized to be distinct biological functions, our findings clearly link the two functions by discovering the novel bifunctional enzyme and further providing the possibility that a hitherto-overlooked antibiotic resistance mechanism mediated by the quorum-quenching enzyme may exist in natural environments and perhaps in clinical settings.
[Mh] Termos MeSH primário: Amidoidrolases/metabolismo
Comamonadaceae/enzimologia
Farmacorresistência Bacteriana
[Mh] Termos MeSH secundário: Acil-Butirolactonas/metabolismo
Amidoidrolases/genética
Antibacterianos/metabolismo
Antibacterianos/farmacologia
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Comamonadaceae/efeitos dos fármacos
Comamonadaceae/genética
Comamonadaceae/fisiologia
Escherichia coli/genética
Escherichia coli/metabolismo
Regulação Bacteriana da Expressão Gênica
Percepção de Quorum
beta-Lactamas/metabolismo
beta-Lactamas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acyl-Butyrolactones); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (beta-Lactams); EC 3.5.- (Amidohydrolases); EC 3.5.1.4 (amidase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171225
[Lr] Data última revisão:
171225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28777819
[Au] Autor:Vasseur MV; Lacroix MZ; Toutain PL; Bousquet-Melou A; Ferran AA
[Ad] Endereço:Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
[Ti] Título:Infection-stage adjusted dose of beta-lactams for parsimonious and efficient antibiotic treatments: A Pasteurella multocida experimental pneumonia in mice.
[So] Source:PLoS One;12(8):e0182863, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, the impact of infection stage on clinically and microbiologically efficacious doses and on antibiotic consumption was assessed during a naturally evolving infectious disease, using an original mouse model of pulmonary infection produced by air-borne contamination. When Pasteurella multocida was administered as pathogenic agent to immunocompetent mice, 60% of the animals exhibited clinical symptoms of pneumonia 2 to 4 days after bacterial contamination of the lungs. Two beta-lactam antibiotics were evaluated: amoxicillin and cefquinome, a fourth generation cephalosporin developed for food animals. First, a pharmacokinetic study was performed in infected mice to determine the exposure to amoxicillin or cefquinome required to treat clinically affected animals, based on the targeted values of PK/PD indices for beta-lactams. We then confirmed that these doses resulted in a 100% clinical cure rate in animals exhibiting clinical signs of infection and harboring a high pathogenic inoculum. More interestingly, we also showed that the same 100% clinical cure could be obtained in our model with 10-fold lower doses in animals at pre-patent stages of infection i.e. when harboring a low pathogenic inoculum. At the group level, antimicrobial drug consumption was reduced by treating animals at an early stage of the infection course with a pre-patent tailored dose. These results suggest that early treatment with a dose suitably adjusted to the stage of infection might help to reduce both overall antibiotic consumption and resistance selection pressure in the animals and in the environment.
[Mh] Termos MeSH primário: Anti-Infecciosos/farmacologia
Infecções por Pasteurella/tratamento farmacológico
Pasteurella multocida/efeitos dos fármacos
Pneumonia Bacteriana/tratamento farmacológico
Infecções Respiratórias/tratamento farmacológico
beta-Lactamas/farmacologia
[Mh] Termos MeSH secundário: Animais
Anti-Infecciosos/administração & dosagem
Feminino
Camundongos
Testes de Sensibilidade Microbiana
Infecções por Pasteurella/microbiologia
beta-Lactamas/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (beta-Lactams)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182863


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[PMID]:28759588
[Au] Autor:Lee YC; Huang YJ; Hung MC; Hung SC; Hsiao CY; Cho HL; Lai LF; Tong SH; Wang JT
[Ad] Endereço:Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
[Ti] Título:Risk factors associated with the development of seizures among adult patients treated with ertapenem: A matched case-control study.
[So] Source:PLoS One;12(7):e0182046, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The purpose of this study is to compare the characteristics of those ertapenem-treated adult patients with and without development of seizures, and identify the associated factors for the development of seizures. METHODS: This retrospective study was conducted at Chia-Yi Christian Hospital from January 2012 to December 2014. Patients developing seizures during their ertapenem treatment course were identified as case patients. Those without seizures who had received ertapenem for at least five days were considered as the pool of control patients. For each case patient, four matched patients from the control pool were randomly selected as the final control group, based on age, gender, and the date of ertapenem prescription. RESULTS: A total of 1706 ertapenem-treated patients were identified, 33 (1.9%) individuals developed seizures with the enrollment of 132 matched control patients. Among these 33 patients, the average age was 79.3 ± 7.5 years, and 20 (60.6%) were male. The mean Charlson co-morbidity score was 4.5 ± 2.4, and the first episode of seizure happened 3.3 ± 2.6 days after receiving ertapenem. In multivariate logistic regression analysis, the independent predictors associated with the development of ertapenem-associated seizures were old stroke (OR, 14.36; 95% CI, 4.38-47.02; p < 0.0001), undergoing brain images within one year prior to the admission (OR, 5.73; 95% CI, 1.78-18.43; p = 0.0034), low hemoglobin level (OR, 3.88; 95% CI, 1.28-12.75; p = 0.0165) and low platelet count (OR, 4,94; 95% CI, 1.56-15.68; p = 0.0067) at presentations, and protective factors against the development of seizures were heart failure (OR, 0.04; 95% CI, 0.00-0.63; p = 0.0222), concomitant use of steroids (OR, 0.19; 95% CI, 0.05-0.77; p = 0.0201), or antiplatelet agents (OR, 0.12; 95% CI, 0.02-0.63, p = 0.0123) with ertapenem. CONCLUSIONS: The development of ertapenem-associated seizures may occur more frequently and much earlier due to its widespread use in treating drug-resistant pathogens, especially when these pathogens emerged worldwide.Our study would help physician to estimate the risk of developing seizure among patients receiving ertapenem.
[Mh] Termos MeSH primário: Antibacterianos/efeitos adversos
Convulsões/etiologia
beta-Lactamas/efeitos adversos
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Antibacterianos/administração & dosagem
Antibacterianos/uso terapêutico
Estudos de Casos e Controles
Feminino
Seres Humanos
Masculino
Convulsões/epidemiologia
beta-Lactamas/administração & dosagem
beta-Lactamas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (beta-Lactams); G32F6EID2H (ertapenem)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182046


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[PMID]:28749999
[Au] Autor:Verdino A; Vigliotta G; Giordano D; Caputo I; Soriente A; De Rosa M; Marabotti A
[Ad] Endereço:Department of Chemistry and Biology "A. Zambelli", University of Salerno, Fisciano (SA), Italy.
[Ti] Título:Synthesis and biological evaluation of the progenitor of a new class of cephalosporin analogues, with a particular focus on structure-based computational analysis.
[So] Source:PLoS One;12(7):e0181563, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We present the synthesis and biological evaluation of the prototype of a new class of cephalosporins, containing an additional isolated beta lactam ring with two phenyl substituents. This new compound is effective against Gram positive microorganisms, with a potency similar to that of ceftriaxone, a cephalosporin widely used in clinics and taken as a reference, and with no cytotoxicity against two different human cell lines, even at a concentration much higher than the minimal inhibitory concentration tested. Additionally, a deep computational analysis has been conducted with the aim of understanding the contribution of its moieties to the binding energy towards several penicillin-binding proteins from both Gram positive and Gram negative bacteria. All these results will help us developing derivatives of this compound with improved chemical and biological properties, such as a broader spectrum of action and/or an increased affinity towards their molecular targets.
[Mh] Termos MeSH primário: Cefalosporinas/química
Cefalosporinas/síntese química
Modelos Moleculares
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Ceftriaxona/síntese química
Ceftriaxona/química
Ceftriaxona/farmacologia
Sobrevivência Celular/efeitos dos fármacos
Cefalosporinas/farmacologia
Bactérias Gram-Negativas/efeitos dos fármacos
Bactérias Gram-Positivas/efeitos dos fármacos
Células Hep G2
Seres Humanos
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Proteínas de Ligação às Penicilinas/farmacologia
Relação Estrutura-Atividade
beta-Lactamas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (Penicillin-Binding Proteins); 0 (beta-Lactams); 75J73V1629 (Ceftriaxone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181563



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