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[PMID]:27671060
[Au] Autor:Pozzi C; De Luca F; Benvenuti M; Poirel L; Nordmann P; Rossolini GM; Mangani S; Docquier JD
[Ad] Endereço:Dipartimento di Biotecnologie, Chimica e Farmacia, Università di Siena, Siena, Italy.
[Ti] Título:Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum ß-Lactamase and Its Complexes with Moxalactam and Imipenem.
[So] Source:Antimicrob Agents Chemother;60(12):7189-7199, 2016 Dec.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BEL-1 is an acquired class A extended-spectrum ß-lactamase (ESBL) found in Pseudomonas aeruginosa clinical isolates from Belgium which is divergent from other ESBLs (maximum identity of 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem, and moxalactam. Crystals of BEL-1 were obtained at pH 5.6, and the structure of native BEL-1 was determined from orthorhombic and monoclinic crystal forms at 1.60-Å and 1.48-Å resolution, respectively. By soaking native BEL-1 crystals, complexes with imipenem (monoclinic form, 1.79-Å resolution) and moxalactam (orthorhombic form, 1.85-Å resolution) were also obtained. In the acyl-enzyme complexes, imipenem and moxalactam differ by the position of the α-substituent and of the carbonyl oxygen (in or out of the oxyanion hole). More surprisingly, the Ω-loop, which includes the catalytically relevant residue Glu166, was found in different conformations in the various subunits, resulting in the Glu166 side chain being rotated out of the active site or even in displacement of its Cα atom up to approximately 10 Å. A BEL-1 variant showing the single Leu162Phe substitution (BEL-2) confers a higher level of resistance to CAZ, CTX, and FEP and shows significantly lower K values than BEL-1, especially with oxyiminocephalosporins. BEL-1 Leu162 is located at the beginning of the Ω-loop and is surrounded by Phe72, Leu139, and Leu148 (contact distances, 3.5 to 3.9 Å). This small hydrophobic cavity could not reasonably accommodate the bulkier Phe162 found in BEL-2 without altering neighboring residues or the Ω-loop itself, thus likely causing an important alteration of the enzyme kinetic properties.
[Mh] Termos MeSH primário: Imipenem/química
Moxalactam/química
beta-Lactamases/química
beta-Lactamases/metabolismo
[Mh] Termos MeSH secundário: Antibacterianos/química
Domínio Catalítico
Ácido Cítrico/química
Cristalografia por Raios X
Dissulfetos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Disulfides); 2968PHW8QP (Citric Acid); 71OTZ9ZE0A (Imipenem); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase BEL-1, Pseudomonas aeruginosa); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160928
[St] Status:MEDLINE


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[PMID]:27629897
[Au] Autor:Bonjean M; Hodille E; Dumitrescu O; Dupieux C; Nkoud Mongo C; Allam C; Beghin M; Paris M; Borrel O; Chardon H; Laurent F; Rasigade JP; Lina G
[Ad] Endereço:IAI, Hospices Civils de Lyon, Lyon, France.
[Ti] Título:Disk Diffusion Testing for Detection of Methicillin-Resistant Staphylococci: Does Moxalactam Improve upon Cefoxitin?
[So] Source:J Clin Microbiol;54(12):2905-2909, 2016 Dec.
[Is] ISSN:1098-660X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Disk diffusion testing is widely used to detect methicillin resistance in staphylococci, and cefoxitin is currently considered the best marker for mecA-mediated methicillin resistance. In low-inoculum diffusion testing (colony suspension at 10 CFU/ml), the addition of moxalactam in combination with cefoxitin has been reported to improve on cefoxitin alone for the detection of methicillin-heteroresistant staphylococci. However, moxalactam is absent from EUCAST and CLSI guidelines, which use high-inoculum diffusion testing (colony suspension at 10 CFU/ml), calling into question the potential interest of including moxalactam in their recommendations. The inhibition zone diameters of cefoxitin and moxalactam, alone and in combination, were evaluated for concordance with mecA and mecC positivity in a large collection of clinical Staphylococcus isolates (611 Staphylococcus aureus, Staphylococcus lugdunensis, and Staphylococcus saprophyticus isolates and 307 coagulase-negative staphylococci other than S. lugdunensis and S. saprophyticus isolates, of which 22% and 53% were mecA-positive, respectively) and in 25 mecC-positive S. aureus isolates using high-inoculum diffusion testing. Receiver operating characteristic, sensitivity, and specificity analyses indicated that the detection of mecA- and mecC-positive and negative isolates did not improve with moxalactam, either alone or in combination with cefoxitin, compared to cefoxitin alone. These findings were similar in both the S. aureus/S. lugdunensis/S. saprophyticus group and in the coagulase-negative staphylococci group. Our results do not support the use of moxalactam as an additional marker of methicillin resistance when testing with high-inoculum disk diffusion.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Cefoxitina/farmacologia
Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação
Moxalactam/farmacologia
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Seres Humanos
Staphylococcus aureus Resistente à Meticilina/genética
Proteínas de Ligação às Penicilinas/genética
Staphylococcus lugdunensis/efeitos dos fármacos
Staphylococcus lugdunensis/genética
Staphylococcus lugdunensis/isolamento & purificação
Staphylococcus saprophyticus/efeitos dos fármacos
Staphylococcus saprophyticus/genética
Staphylococcus saprophyticus/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Penicillin-Binding Proteins); 0 (mecA protein, Staphylococcus aureus); 6OEV9DX57Y (Cefoxitin); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160916
[St] Status:MEDLINE


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[PMID]:27266357
[Au] Autor:Quan JJ; Wang Y; Ji JS; Wang YF; Wang HP; Xu YC; Yu YS
[Ad] Endereço:Sir Run Run Shaw Hospital, the Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.
[Ti] Título:[The activity of moxalactam against Enterobacteriaceae and anaerobia in vitro].
[So] Source:Zhonghua Yi Xue Za Zhi;96(18):1459-64, 2016 May 17.
[Is] ISSN:0376-2491
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To observe the antibacterial activity of moxalactam against Enterobacteriaceae bacteria and anaerobic bacteria in vitro, and to compare with other antibacterial drugs, for providing experimental basis for the clinical application of moxalactam. METHODS: Minimum inhibitory concentrations (MICs) of moxalactam and other antibacterial agents against 491 Enterobacteriaceae spp. and anaerobic spp.collecting from clinical settings were determined by agar dilution methods and E-test strips according to the Clinical and Laboratory Standards Institute (CLSI)(2014). RESULTS: Moxalactam showed great antibacterial activity to Enterobacteriaceae spp., including ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp., with the MIC(50), MIC(90), and susceptibility rates of 0.25-4 mg/L, 0.5-8 mg/L, and >90%, respectively. The susceptibility rates of Enterobacteriaceae with ESBLs-producing or non-ESBLs-producing to imipenem and meropenem were both higher than 90%. The susceptibility rates of ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.to piperacillin/tazobactam and cefoperazone/sulbactam were 90%, 68%, 53% and 76%, 66%, 76.6%, respectively, while the susceptibility rates of non-ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.were all more than 95%. The susceptibility rates of Enterobacter spp. and other Enterobacter to piperacillin/tazobactam were 80%, 80%and that to cefoperazone/sulbactam were 80%, 76.7%, respectively.The MICs range of moxalactam on anaerobic spp.was from ≤0.064 to >256 mg/L, while MIC(50) was 2 mg/L and MIC(90) was 64 mg/L. CONCLUSIONS: Moxalactam showed well activity against ESBLs-producing and non-ESBLs-producing Enterobacteriaceae and anaerobia.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Enterobacteriaceae/efeitos dos fármacos
Moxalactam/farmacologia
[Mh] Termos MeSH secundário: Bactérias Anaeróbias/efeitos dos fármacos
Cefoperazona/farmacologia
Escherichia coli/efeitos dos fármacos
Imipenem/farmacologia
Klebsiella pneumoniae/efeitos dos fármacos
Testes de Sensibilidade Microbiana
Ácido Penicilânico/análogos & derivados
Ácido Penicilânico/farmacologia
Piperacilina/farmacologia
Proteus/efeitos dos fármacos
Tienamicinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Thienamycins); 157044-21-8 (piperacillin, tazobactam drug combination); 71OTZ9ZE0A (Imipenem); 7U75I1278D (Cefoperazone); 87-53-6 (Penicillanic Acid); FV9J3JU8B1 (meropenem); VUF6C936Z3 (Moxalactam); X00B0D5O0E (Piperacillin)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160609
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0376-2491.2016.18.015


  4 / 951 MEDLINE  
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[PMID]:26953118
[Au] Autor:Jost G; Bloemberg GV; Hombach M
[Ad] Endereço:1​ Institut Medizinische Mikrobiologie, Universität Zürich, Zürich, Switzerland 2​ Dianalabs, Geneva, Switzerland.
[Ti] Título:Improved sensitivity for meticillin resistance detection in coagulase-negative staphylococci by moxalactam antibiotic discs or a cefoxitin investigation zone.
[So] Source:J Med Microbiol;65(6):566-8, 2016 Jun.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Cefoxitina/farmacologia
Resistência a Meticilina
Testes de Sensibilidade Microbiana/métodos
Moxalactam/farmacologia
Staphylococcus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Técnicas Bacteriológicas
Coagulase/metabolismo
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Coagulase); 6OEV9DX57Y (Cefoxitin); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170126
[Lr] Data última revisão:
170126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160309
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000243


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[PMID]:26282421
[Au] Autor:Tada T; Nhung PH; Miyoshi-Akiyama T; Shimada K; Phuong DM; Anh NQ; Ohmagari N; Kirikae T
[Ad] Endereço:Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
[Ti] Título:IMP-51, a novel IMP-type metallo-ß-lactamase with increased doripenem- and meropenem-hydrolyzing activities, in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate.
[So] Source:Antimicrob Agents Chemother;59(11):7090-3, 2015 Nov.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A meropenem-resistant Pseudomonas aeruginosa isolate was obtained from a patient in a medical setting in Hanoi, Vietnam. The isolate was found to have a novel IMP-type metallo-ß-lactamase, IMP-51, which differed from IMP-7 by an amino acid substitution (Ser262Gly). Escherichia coli expressing blaIMP-51 showed greater resistance to cefoxitin, meropenem, and moxalactam than E. coli expressing blaIMP-7. The amino acid residue at position 262 was located near the active site, proximal to the H263 Zn(II) ligand.
[Mh] Termos MeSH primário: Carbapenêmicos/farmacologia
Pseudomonas aeruginosa/efeitos dos fármacos
Tienamicinas/farmacologia
beta-Lactamases/metabolismo
[Mh] Termos MeSH secundário: Cefoxitina/farmacologia
Escherichia coli/efeitos dos fármacos
Escherichia coli/enzimologia
Testes de Sensibilidade Microbiana
Moxalactam/farmacologia
Pseudomonas aeruginosa/enzimologia
beta-Lactamases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carbapenems); 0 (Thienamycins); 6OEV9DX57Y (Cefoxitin); BHV525JOBH (doripenem); EC 3.5.2.6 (beta-Lactamases); FV9J3JU8B1 (meropenem); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160501
[Lr] Data última revisão:
160501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150819
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.01611-15


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[PMID]:26055361
[Au] Autor:Oguri T; Ishii Y; Shimizu-Ibuka A
[Ad] Endereço:Department of Science, Yamagata University, Yamagata, Japan.
[Ti] Título:Conformational Change Observed in the Active Site of Class C ß-Lactamase MOX-1 upon Binding to Aztreonam.
[So] Source:Antimicrob Agents Chemother;59(8):5069-72, 2015 Aug.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We solved the crystal structure of the class C ß-lactamase MOX-1 complexed with the inhibitor aztreonam at 1.9Å resolution. The main-chain oxygen of Ser315 interacts with the amide nitrogen of aztreonam. Surprisingly, compared to that in the structure of free MOX-1, this main-chain carboxyl changes its position significantly upon binding to aztreonam. This result indicates that the interaction between MOX-1 and ß-lactams can be accompanied by conformational changes in the B3 ß-strand main chain.
[Mh] Termos MeSH primário: Aztreonam/química
Proteínas de Bactérias/ultraestrutura
Domínio Catalítico
Moxalactam/antagonistas & inibidores
beta-Lactamases/ultraestrutura
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Antibacterianos/farmacologia
Aztreonam/farmacologia
Proteínas de Bactérias/genética
Sítios de Ligação
Dióxido de Carbono/química
Cristalografia por Raios X
Farmacorresistência Bacteriana Múltipla/genética
Klebsiella pneumoniae/efeitos dos fármacos
Klebsiella pneumoniae/genética
Testes de Sensibilidade Microbiana
Modelos Moleculares
Moxalactam/química
Moxalactam/farmacologia
Conformação Proteica
Especificidade por Substrato
beta-Lactamases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 142M471B3J (Carbon Dioxide); 14485-07-5 (carboxyl radical); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase Mox-1, Klebsiella pneumoniae); G2B4VE5GH8 (Aztreonam); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150610
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.04428-14


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[PMID]:24956910
[Au] Autor:Ito A; Tatsumi Y; Wajima T; Nakamura R; Tsuji M
[Ti] Título:Potent antibacterial activities of latamoxef (moxalactam) against ESBL producing Enterobacteriaceae analyzed by Monte Carlo simulation.
[So] Source:Jpn J Antibiot;67(2):109-22, 2014 Apr.
[Is] ISSN:0368-2781
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Latamoxef (LMOX, Moxalactam) is one of the beta-lactam antibiotics which is stable against beta-lactamase. In this study, the antibacterial activity of LMOX was investigated, and Monte Carlo simulation was conducted to determine the appropriate dosing regimens of LMOX against extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. The probability of target attainment (PTA) was analyzed at 40% and 70% of time above minimum inhibitory concentration (MIC) (time above MIC, T(>MIC)) for bacteriostatic and bactericidal effect respectively. All the tested regimens achieved 85% of PTA at 40% of T(>MIC) against ESBL producing Escherichia coli, and all the tested regimens except 1g q12h with 1 hour infusion achieved 85% of PTA at 40% of T(>MIC) against ESBL producing Klebsiella pneumoniae. The effective regimens to achieve 85% of PTA at 70% of T(>MIC )against E. coli were lg ql2h with 4 hours infusion, lg q8h with 1-4 hours infusion, 2g ql2h with 2-4 hours infusion, and lg q6h with 1-4 hours infusion. The effective regimens to achieve 85% of PTA at 70% of T(>MIC) against K. pneumoniae were 1g q8h with 3-4 hours infusion and 1g q6h with 1-4 hours infusion. These results of pharmacokinetics/pharmacodynamics (PK/PD) modeling showed the potent efficacy of LMOX against bacterial infections caused by ESBL producing Enterobacteriaceae.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Enterobacteriaceae/efeitos dos fármacos
Moxalactam/farmacologia
beta-Lactamases/biossíntese
[Mh] Termos MeSH secundário: Seres Humanos
Testes de Sensibilidade Microbiana
Método de Monte Carlo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); EC 3.5.2.6 (beta-Lactamases); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1407
[Cu] Atualização por classe:161116
[Lr] Data última revisão:
161116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140625
[St] Status:MEDLINE


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[PMID]:24777102
[Au] Autor:Oguri T; Furuyama T; Okuno T; Ishii Y; Tateda K; Bonomo RA; Shimizu-Ibuka A
[Ad] Endereço:Department of Science, Yamagata University, Yamagata, Japan.
[Ti] Título:Crystal structure of Mox-1, a unique plasmid-mediated class C ß-lactamase with hydrolytic activity towards moxalactam.
[So] Source:Antimicrob Agents Chemother;58(7):3914-20, 2014 Jul.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mox-1 is a unique plasmid-mediated class C ß-lactamase that hydrolyzes penicillins, cephalothin, and the expanded-spectrum cephalosporins cefepime and moxalactam. In order to understand the unique substrate profile of this enzyme, we determined the X-ray crystallographic structure of Mox-1 ß-lactamase at a 1.5-Å resolution. The overall structure of Mox-1 ß-lactamase resembles that of other AmpC enzymes, with some notable exceptions. First, comparison with other enzymes whose structures have been solved reveals significant differences in the composition of amino acids that make up the hydrogen-bonding network and the position of structural elements in the substrate-binding cavity. Second, the main-chain electron density is not observed in two regions, one containing amino acid residues 214 to 216 positioned in the Ω loop and the other in the N terminus of the B3 ß-strand corresponding to amino acid residues 303 to 306. The last two observations suggest that there is significant structural flexibility of these regions, a property which may impact the recognition and binding of substrates in Mox-1. These important differences allow us to propose that the binding of moxalactam in Mox-1 is facilitated by the avoidance of steric clashes, indicating that a substrate-induced conformational change underlies the basis of the hydrolytic profile of Mox-1 ß-lactamase.
[Mh] Termos MeSH primário: Antibacterianos/metabolismo
Proteínas de Bactérias/química
Moxalactam/metabolismo
beta-Lactamases/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Domínio Catalítico
Cristalografia por Raios X
Escherichia coli/enzimologia
Escherichia coli/genética
Hidrólise
Modelos Moleculares
Dados de Sequência Molecular
Mutagênese Sítio-Dirigida
Plasmídeos/genética
Conformação Proteica
beta-Lactamases/genética
beta-Lactamases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase Mox-1, Klebsiella pneumoniae); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140430
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.02363-13


  9 / 951 MEDLINE  
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[PMID]:22825119
[Au] Autor:Yuan Q; He L; Ke H
[Ad] Endereço:Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina, USA.
[Ti] Título:A potential substrate binding conformation of ß-lactams and insight into the broad spectrum of NDM-1 activity.
[So] Source:Antimicrob Agents Chemother;56(10):5157-63, 2012 Oct.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:New Delhi metallo-ß-lactamase 1 (NDM-1) is a key enzyme that the pathogen Klebsiella pneumonia uses to hydrolyze almost all ß-lactam antibiotics. It is currently unclear why NDM-1 has a broad spectrum of activity. Docking of the representatives of the ß-lactam families into the active site of NDM-1 is reported here. All the ß-lactams naturally fit the NDM-1 pocket, implying that NDM-1 can accommodate the substrates without dramatic conformation changes. The docking reveals two major binding modes of the ß-lactams, which we tentatively name the S (substrate) and I (inhibitor) conformers. In the S conformers of all the ß-lactams, the amide oxygen and the carboxylic group conservatively interact with two zinc ions, while the substitutions on the fused rings show dramatic differences in their conformations and positions. Since the bridging hydroxide ion/water in the S conformer is at the position for the nucleophilic attack, the S conformation may simulate the true binding of a substrate to NDM-1. The I conformer either blocks or displaces the bridging hydroxide ion/water, such as in the case of aztreonam, and is thus inhibitory. The docking also suggests that substitutions on the ß-lactam ring are required for ß-lactams to bind in the S conformation, and therefore, small ß-lactams such as clavulanic acid would be inhibitors of NDM-1. Finally, our docking shows that moxalactam uses its tyrosyl-carboxylic group to compete with the S conformer and would thus be a poor substrate of NDM-1.
[Mh] Termos MeSH primário: Klebsiella pneumoniae/enzimologia
beta-Lactamases/química
beta-Lactamases/metabolismo
beta-Lactamas/metabolismo
beta-Lactamas/farmacologia
[Mh] Termos MeSH secundário: Domínio Catalítico
Ácido Clavulânico/metabolismo
Ácido Clavulânico/farmacologia
Klebsiella pneumoniae/efeitos dos fármacos
Moxalactam/metabolismo
Moxalactam/farmacologia
Ligação Proteica
Conformação Proteica
beta-Lactamases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (beta-Lactams); 23521W1S24 (Clavulanic Acid); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase NDM-1); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1302
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120725
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.05896-11


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Fotocópia
[PMID]:21644068
[Au] Autor:Özel G; Aslan V; Bahar Erdem G; Çagatay M; Sencan I; Mert A
[Ad] Endereço:Ministry of Health Diskapi Yildirim Beyazit Training and Research Hospital, Microbiology and Clinical Microbiology Clinics, Ankara, Turkey. ozel78@yahoo.com
[Ti] Título:[Comparison of oxacillin, cefoxitin, ceftizoxime, and moxalactam disk diffusion methods for detection of methicillin susceptibility in staphylococci].
[Ti] Título:Stafilokoklarda Metisilin Duyarliliginin Belirlenmesinde Oksasilin, Sefoksitin, Seftizoksim ve Moksalaktam Disk Difüzyon Yöntemlerinin Karsilastirilmasi.
[So] Source:Mikrobiyol Bul;45(2):258-65, 2011 Apr.
[Is] ISSN:0374-9096
[Cp] País de publicação:Turkey
[La] Idioma:tur
[Ab] Resumo:Penicillin binding protein 2a/2' (PBP2a/PBP2') which is encoded by the mecA gene, is responsible for the methicillin resistance in staphylococci. Detection of methicillin resistance with phenotypic methods is still a problem especially because of heterogenous expression of mecA gene. Although mecA gene determination by polymerase chain reaction is considered as the gold standard method, molecular tests are not easily applied in all routine laboratories. Thus, for the rapid and accurate diagnosis of MRSA strains, easy and practical phenotypic tests are still required. This study was conducted to compare the oxacillin (OX), cefoxitin (CFX), ceftizoxime (CZX), and moxolactam (MOX) susceptibility testing by disk diffusion method for the detection of methicillin resistance in staphylococci. A total of 247 staphylococci (125 Staphylococcus aureus and 122 coagulase-negative staphylococci; CNS) isolated from various clinical specimens (114 wound and soft tissue materials, 51 urine, 48 blood, 30 respiratory tract, and four other samples) of inpatients and outpatients, were included in this study. PBP2a latex agglutination test was used as the reference method for the recognition of methicillin resistance; four antibiotic disks tested and sensitivity, specificity, positive and negative predictive values (PPV and NPV) were determined for each of them. According to PBP2a latex agglutination test 66 (54.1%) of CNS and 53 (42.4%) of S.aureus isolates were found methicillin- resistant. OX and MOX disks detected 113 (63 CNS and 50 S.aureus) methicillin-resistant strain out of 119 PBP2a positive isolates, where CFX and CZX disks detected 110 (60 CNS and 50 S.aureus) of them. Among 128 PBP2a negative isolates, 123 (52 CNS and 71 S.aureus) were detected as susceptible with OX, 127 (55 CNS and 72 S.aureus) with CFX and CZX, 126 (54 CNS and 72 S.aureus) with MOX. According to these results, the sensitivities and specificities of OX, CFX, CZX, and MOX disks were; 95.4% and 92.8%, 90.9% and 98.2%, 90.9% and 98.2%, 95.4% and 96.4%, respectively for CNS and 94.3% and 98.6%, 94.3% and 100%, 94.3% and 100%, 94.3% and 100%, respectively for S.aureus. The difference between sensitivities and specificities of tested antibiotic disks were not found statistically significant. In conclusion, due to the problems in detection of methicillin resistance with phenotypic methods, the use of different mecA gene-inducing antibiotic disks at the same time, and utilization of molecular methods as reference method might be suggested, when a discordance is observed between the antibiotic disks.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos
Meticilina/farmacologia
Staphylococcus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Cefoxitina/farmacologia
Ceftizoxima/farmacologia
Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/normas
Seres Humanos
Testes de Fixação do Látex
Moxalactam/farmacologia
Oxacilina/farmacologia
Proteínas de Ligação às Penicilinas
Valor Preditivo dos Testes
Sensibilidade e Especificidade
Infecções Estafilocócicas/microbiologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Penicillin-Binding Proteins); 6OEV9DX57Y (Cefoxitin); C43C467DPE (Ceftizoxime); Q91FH1328A (Methicillin); UH95VD7V76 (Oxacillin); VUF6C936Z3 (Moxalactam)
[Em] Mês de entrada:1110
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110607
[St] Status:MEDLINE



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