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[PMID]:28292660
[Au] Autor:Wang L; Nakamura H; Kage-Nakadai E; Hara-Kudo Y; Nishikawa Y
[Ad] Endereço:Dalian University of Technology, School of Life Science and Biotechnology, Dalian 116024, China; Osaka City University, Graduate School of Human Life Science, Osaka 558-8585, Japan.
[Ti] Título:Prevalence, antimicrobial resistance and multiple-locus variable-number tandem-repeat analysis profiles of diarrheagenic Escherichia coli isolated from different retail foods.
[So] Source:Int J Food Microbiol;249:44-52, 2017 May 16.
[Is] ISSN:1879-3460
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Diarrheagenic E. coli (DEC) isolates were recovered from local retail markets and the Osaka Municipal Central Wholesale Market in Japan. Retail food samples were collected for analysis in Osaka Japan from 2005 to 2008 and consisted of 32 beef, 28 pork, 20 poultry, 136 fish, 66 fruits and vegetables and 51 ready-to-eat (RTE) food samples. A total of 82 DEC strains were recovered from 64 (19%) food samples with the highest prevalence in poultry (100%, 20/20), followed by pork (54%, 15/28), beef (28%, 9/32), fruits and vegetables (12%, 8/66), fish (6.6%, 9/136) and RTE foods (5.9%, 3/51). Most of the strains belonged to E. coli possessing the enteroaggregative E. coli (EAEC) heat-stable enterotoxin 1 (EAST1) gene (EAST1EC; n=62, P<0.0001) and enteropathogenic E. coli (EPEC; n=16, P<0.01), whereas only 1 strain belonged to Shiga toxin-producing E. coli (STEC), 1 to EAEC and 2 to enterotoxigenic E. coli (ETEC) strains. Of the 82 DEC isolates, 22 O and 13H serogroups were detected, including some specific serogroups (O91, O103, O115, O119, O126, and O157) which have been associated with human diarrheal infections. Phylogenetic group A and B1 were predominant among the DEC isolates. Antimicrobial resistance to tetracycline was most common (49%), followed by nalidixic acid (28%), ampicillin (24%), sulfamethoxazole/trimethoprim (20%), and cephalothin (18%). All isolates were susceptible to aztreonam. Of the resistant strains, 44% (22/50) demonstrated resistance to >3 antimicrobial agents. Isolates resistant to >5 antimicrobials were only found in the meat samples, while isolates from the fruits and vegetables as well as RTE foods showed resistance to only 1 or 2 antimicrobial agents. Sixty one percent of EAST1EC, 56% of EPEC and all of the EAEC and ETEC were resistant to at least 1 antimicrobial agent. Multiple-locus variable-number tandem repeat analysis (MLVA) was used in this study for genotyping of DEC. The 82 isolates collected for this study showed 77 distinct MLVA profiles located among 3 branches. The Simpson's Index of Diversity (D) was 99.9% at its highest. The high diversity of these food strains would suggest their originating from a variety of sources and environments. In conclusion, retail food samples in Japan were contaminated with DEC; EAST1EC, a putative DEC, were detected at high rates in poultry, pork and beef. Isolates resistant to >3 antimicrobials were found only in raw meat and fish. Food animals may act as the reservoir for multi-resistant bacteria. Due to the finding that nearly 1/3 of EAST1EC strains were resistant to >3 antimicrobials, additional surveillance for EAST1EC should be initiated.
[Mh] Termos MeSH primário: Escherichia coli Enteropatogênica/isolamento & purificação
Escherichia coli Enterotoxigênica/isolamento & purificação
Enterotoxinas/metabolismo
Contaminação de Alimentos/análise
Frutas/microbiologia
Carne Vermelha/microbiologia
Alimentos Marinhos/microbiologia
Verduras/microbiologia
[Mh] Termos MeSH secundário: Ampicilina/farmacologia
Animais
Antibacterianos/farmacologia
Bovinos
Cefalotina/farmacologia
Escherichia coli Enteropatogênica/efeitos dos fármacos
Escherichia coli Enteropatogênica/genética
Escherichia coli Enterotoxigênica/efeitos dos fármacos
Escherichia coli Enterotoxigênica/genética
Infecções por Escherichia coli/microbiologia
Proteínas de Escherichia coli/metabolismo
Microbiologia de Alimentos
Seres Humanos
Japão
Testes de Sensibilidade Microbiana
Repetições Minissatélites/genética
Ácido Nalidíxico/farmacologia
Prevalência
Suínos
Tetraciclina/farmacologia
Combinação Trimetoprima e Sulfametoxazol/farmacologia
Fatores de Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Enterotoxins); 0 (Escherichia coli Proteins); 0 (Virulence Factors); 3B91HWA56M (Nalidixic Acid); 7C782967RD (Ampicillin); 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination); F8VB5M810T (Tetracycline); R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170316
[St] Status:MEDLINE


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[PMID]:27543129
[Au] Autor:Kang CH; Shin Y; Jang S; Jung Y; So JS
[Ad] Endereço:Department of Biological Engineering, Inha University, 100 Inha-ro, Nam-gu, Incheon, 402-751, South Korea.
[Ti] Título:Antimicrobial susceptibility of Vibrio alginolyticus isolated from oyster in Korea.
[So] Source:Environ Sci Pollut Res Int;23(20):21106-21112, 2016 Oct.
[Is] ISSN:1614-7499
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Pathogenic Vibrio alginolyticus, a cause of severe infection in shellfish, as well as in humans, has been found at high frequency around all coastal areas of Korea. The aim of this study was to determine the occurrence of V. alginolyticus, to identify the strains isolated from oysters in West Sea, and to investigate their antimicrobial resistance profiles. Biochemical analyses of the 90 initially recovered presumptive V. alginolyticus colonies indicated that 16 isolates were V. alginolyticus. PCR analysis to detect the presence of the gyrB gene confirmed that 15 (93.8 %) of the 16 isolates were V. alginolyticus. These 15 isolates had the following profiles of resistance against 16 antibiotics: all isolates were resistant to ampicillin and vancomycin, and 26.7 % of the isolates exhibited resistance to cephalothin. A large number of isolates showed intermediate resistance to erythromycin (100 %) and rifampin (73.3 %). Five (33.3 %) of the V. alginolyticus isolates demonstrated multiple resistance to at least three antimicrobials.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Farmacorresistência Bacteriana
Ostreidae/microbiologia
Frutos do Mar/microbiologia
Vibrio alginolyticus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ampicilina/farmacologia
Animais
Cefalotina/farmacologia
Eritromicina/farmacologia
Genes Bacterianos
República da Coreia
Rifampina
Vancomicina/farmacologia
Vibrio alginolyticus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 63937KV33D (Erythromycin); 6Q205EH1VU (Vancomycin); 7C782967RD (Ampicillin); R72LW146E6 (Cephalothin); VJT6J7R4TR (Rifampin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160821
[St] Status:MEDLINE


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[PMID]:27364644
[Au] Autor:Udoh A; Effa EE; Oduwole O; Okusanya BO; Okafo O
[Ad] Endereço:Obstetrics and Gynaecology, College of Medical Sciences, University of Calabar, Calabar, Cross River State, Nigeria.
[Ti] Título:Antibiotics for treating septic abortion.
[So] Source:Cochrane Database Syst Rev;7:CD011528, 2016 Jul 01.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A septic abortion refers to any abortion (spontaneous or induced) complicated by upper genital tract infection including endometritis or parametritis. The mainstay of treatment of septic abortion is antibiotic therapy alone or in combination with evacuation of retained products of conception. Regimens including broad-spectrum antibiotics are routinely recommended for treatment. However, there is no consensus on the most effective antibiotics alone or in combination to treat septic abortion. This review aimed to bridge this gap in knowledge to inform policy and practice. OBJECTIVES: To review the effectiveness of various individual antibiotics or antibiotic regimens in the treatment of septic abortion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and POPLINE using the following keywords: 'Abortion', 'septic abortion', 'Antibiotics', 'Infected abortion', 'postabortion infection'. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 19 April, 2016. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) and non-RCTs that compared antibiotic(s) to another antibiotic(s), irrespective of route of administration, dosage, and duration as well as studies comparing antibiotics alone with antibiotics in combination with other interventions such as dilation and curettage (D&C). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included trials. We resolved disagreements through consultation with a third author. One review author entered extracted data into Review Manager 5.3, and a second review author cross-checked the entry for accuracy. MAIN RESULTS: We included 3 small RCTs involving 233 women that were conducted over 3 decades ago.Clindamycin did not differ significantly from penicillin plus chloramphenicol in reducing fever in all women (mean difference (MD) -12.30, 95% confidence interval (CI) -25.12 to 0.52; women = 77; studies = 1). The evidence for this was of moderate quality. "Response to treatment was evaluated by the patient's 'fever index' expressed in degree-hour and defined as the total quantity of fever under the daily temperature curve with 99°F (37.2°C) as the baseline".There was no difference in duration of hospitalisation between clindamycin and penicillin plus chloramphenicol. The mean duration of hospital stay for women in each group was 5 days (MD 0.00, 95% CI -0.54 to 0.54; women = 77; studies = 1).One study evaluated the effect of penicillin plus chloramphenicol versus cephalothin plus kanamycin before and after D&C. Response to therapy was evaluated by "the time from start of antibiotics until fever lysis and time from D&C until patients become afebrile". Low-quality evidence suggested that the effect of penicillin plus chloramphenicol on fever did not differ from that of cephalothin plus kanamycin (MD -2.30, 95% CI -17.31 to 12.71; women = 56; studies = 1). There was no significant difference between penicillin plus chloramphenicol versus cephalothin plus kanamycin when D&C was performed during antibiotic therapy (MD -1.00, 95% CI -13.84 to 11.84; women = 56; studies = 1). The quality of evidence was low.A study with unclear risk of bias showed that the time for fever resolution (MD -5.03, 95% CI -5.77 to -4.29; women = 100; studies = 1) as well as time for resolution of leukocytosis (MD -4.88, 95% CI -5.98 to -3.78; women = 100; studies = 1) was significantly lower with tetracycline plus enzymes compared with intravenous penicillin G.Treatment failure and adverse events occurred infrequently, and the difference between groups was not statistically significant. AUTHORS' CONCLUSIONS: We found no strong evidence that intravenous clindamycin alone was better than penicillin plus chloramphenicol for treating women with septic abortion. Similarly, available evidence did not suggest that penicillin plus chloramphenicol was better than cephalothin plus kanamycin for the treatment of women with septic abortion. Tetracyline enzyme antibiotic appeared to be more effective than intravenous penicillin G in reducing the time to fever defervescence, but this evidence was provided by only one study at low risk of bias.There is a need for high-quality RCTs providing reliable evidence for treatments of septic abortion with antibiotics that are currently in use. The three included studies were carried out over 30 years ago. There is also a need to include institutions in low-resource settings, such as sub-Saharan Africa, Latin America and the Caribbean, and South Asia, with a high burden of abortion and health systems challenges.
[Mh] Termos MeSH primário: Aborto Séptico/tratamento farmacológico
Antibacterianos/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Cefalotina/uso terapêutico
Cloranfenicol/uso terapêutico
Clindamicina/uso terapêutico
Quimioterapia Combinada
Feminino
Seres Humanos
Canamicina/uso terapêutico
Tempo de Internação
Penicilinas/uso terapêutico
Gravidez
Ensaios Clínicos Controlados Aleatórios como Assunto
Tetraciclina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Penicillins); 3U02EL437C (Clindamycin); 59-01-8 (Kanamycin); 66974FR9Q1 (Chloramphenicol); F8VB5M810T (Tetracycline); R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160802
[Lr] Data última revisão:
160802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160702
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD011528.pub2


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[PMID]:26918257
[Au] Autor:Tripathi R; Nair NN
[Ad] Endereço:Department of Chemistry, Indian Institute of Technology Kanpur , Kanpur 208016, India.
[Ti] Título:Deacylation Mechanism and Kinetics of Acyl-Enzyme Complex of Class C ß-Lactamase and Cephalothin.
[So] Source:J Phys Chem B;120(10):2681-90, 2016 Mar 17.
[Is] ISSN:1520-5207
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the molecular details of antibiotic resistance by the bacterial enzymes ß-lactamases is vital for the development of novel antibiotics and inhibitors. In this spirit, the detailed mechanism of deacylation of the acyl-enzyme complex formed by cephalothin and class C ß-lactamase is investigated here using hybrid quantum-mechanical/molecular-mechanical molecular dynamics methods. The roles of various active-site residues and substrate in the deacylation reaction are elucidated. We identify the base that activates the hydrolyzing water molecule and the residue that protonates the catalytic serine (Ser64). Conformational changes in the active sites and proton transfers that potentiate the efficiency of the deacylation reaction are presented. We have also characterized the oxyanion holes and other H-bonding interactions that stabilize the reaction intermediates. Together with the kinetic and mechanistic details of the acylation reaction, we analyze the complete mechanism and the overall kinetics of the drug hydrolysis. Finally, the apparent rate-determining step in the drug hydrolysis is scrutinized.
[Mh] Termos MeSH primário: Cefalotina/metabolismo
Simulação de Dinâmica Molecular
beta-Lactamases/metabolismo
[Mh] Termos MeSH secundário: Acilação
Cefalotina/química
Ligações de Hidrogênio
Hidrólise
Cinética
Conformação Molecular
beta-Lactamases/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 3.5.2.6 (beta-Lactamases); R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160227
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jpcb.5b11623


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[PMID]:26764340
[Au] Autor:Roberts DM; Ranganathan D; Wallis SC; Varghese JM; Kark A; Lipman J; Roberts JA
[Ad] Endereço:Burns, Trauma & Critical Care Research Centre, School of Medicine, The University of Queensland, Butterfield Street, Herston, Queensland, Australia Medical School, Australian National University, Acton, ACT, Australia darren.roberts@uq.edu.au.
[Ti] Título:Pharmacokinetics of Intraperitoneal Cefalothin and Cefazolin in Patients Being Treated for Peritoneal Dialysis-Associated Peritonitis.
[So] Source:Perit Dial Int;36(4):415-20, 2016 Jul-Aug.
[Is] ISSN:1718-4304
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: ♦ BACKGROUND: The standard treatment of peritoneal dialysis (PD)-associated peritonitis (PD-peritonitis) is intraperitoneal (IP) administration of antibiotics. Only limited data on the pharmacokinetics and appropriateness of contemporary dose recommendations of IP cefalothin and cefazolin exist. The aim of this study was to describe the pharmacokinetics of IP cefalothin and cefazolin in patients treated for PD-peritonitis. ♦ METHODS: As per international guidelines, IP cefalothin or cefazolin 15 mg/kg once daily was dosed with gentamicin in a 6-hour dwell to patients with PD-peritonitis during routine care. Serial plasma and PD effluent samples were collected over the first 24 hours of therapy. Antibiotic concentrations were quantified using a validated chromatographic method with pharmacokinetic analysis performed using a non-compartmental approach. ♦ RESULTS: Nineteen patients were included (cefalothin n = 8, cefazolin n = 11). The median bioavailability for both antibiotics exceeded 92%, but other pharmacokinetic parameters varied markedly between antibiotics. Both antibiotics achieved high PD effluent concentrations throughout the antibiotic dwell. Cefazolin had a smaller volume of distribution compared with cefalothin (14 vs 40 L, p = 0.003). The median trough total plasma antibiotic concentration for cefazolin and cefalothin during the dwell differed (plasma 56 vs 13 mg/L, p < 0.0001) despite a similar concentration in PD effluent (37 vs 38 mg/L, p = 0.58). Lower antibiotic concentrations were noted during PD dwells not containing antibiotic, particularly cefalothin, which was frequently undetectable in plasma and PD effluent. The median duration that the unbound antibiotic concentration was above the minimum inhibitory concentration (MIC) was approximately 13% (plasma) and 25% (IP) for cefalothin, and 100% (plasma and IP) for cefazolin, of the dosing interval. ♦ CONCLUSIONS: When IP cefalothin or cefazolin is allowed to dwell for 6 hours, sufficient PD effluent concentrations are present for common pathogens during this time. However, with once-daily IP dosing, in contrast to cefazolin, there is a risk of subtherapeutic plasma and PD effluent cefalothin concentrations, so more frequent dosing may be required.
[Mh] Termos MeSH primário: Antibacterianos/farmacocinética
Cefazolina/farmacocinética
Cefalotina/farmacocinética
Falência Renal Crônica/terapia
Diálise Peritoneal/efeitos adversos
Peritonite/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Antibacterianos/administração & dosagem
Disponibilidade Biológica
Cefazolina/administração & dosagem
Cefalotina/administração & dosagem
Feminino
Gentamicinas/administração & dosagem
Seres Humanos
Masculino
Meia-Idade
Peritonite/etiologia
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Gentamicins); IHS69L0Y4T (Cefazolin); R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170316
[Lr] Data última revisão:
170316
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160115
[St] Status:MEDLINE
[do] DOI:10.3747/pdi.2015.00008


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[PMID]:26760994
[Au] Autor:Manosalva L; Mutis A; Urzúa A; Fajardo V; Quiroz A
[Ad] Endereço:Laboratorio de Productos Naturales, Instituto de la Patagonia, Universidad de Magallanes, Punta Arenas 6210427, Chile. Loreto.manosalva@umag.cl.
[Ti] Título:Antibacterial Activity of Alkaloid Fractions from Berberis microphylla G. Forst and Study of Synergism with Ampicillin and Cephalothin.
[So] Source:Molecules;21(1):76, 2016 Jan 11.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Berberis microphylla is a native plant that grows in Patagonia and is commonly used by aboriginal ethnic groups in traditional medicine as an antiseptic for different diseases. The present study evaluated the antibacterial and synergistic activity of alkaloid extracts of B. microphylla leaves, stems and roots used either individually or in combination with antibiotics against Gram-positive and Gram-negative bacteria. The in vitro antibacterial activities of leaf, stem and root alkaloid extracts had significant activity only against Gram-positive bacteria. Disc diffusion tests demonstrated that the root extract showed similar activity against B. cereus and S. epidermidis compared to commercial antibiotics, namely ampicillin and cephalothin, and pure berberine, the principal component of the alkaloid extracts, was found to be active only against S. aureus and S. epidermidis with similar activity to that of the root extract. The minimum inhibitory concentrations (MICs) of the alkaloid extracts ranged from 333 to 83 µg/mL, whereas minimum bactericidal concentrations (MBCs) varied from 717 to 167 µg/mL. In addition, synergistic or indifferent effects between the alkaloid extracts and antibiotics against bacterial strains were confirmed.
[Mh] Termos MeSH primário: Ampicilina/farmacologia
Antibacterianos/farmacologia
Alcaloides de Berberina/farmacologia
Berberis/química
Cefalotina/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/isolamento & purificação
Alcaloides de Berberina/isolamento & purificação
Sinergismo Farmacológico
Bactérias Gram-Negativas/efeitos dos fármacos
Bactérias Gram-Negativas/crescimento & desenvolvimento
Bactérias Gram-Positivas/efeitos dos fármacos
Bactérias Gram-Positivas/crescimento & desenvolvimento
Testes de Sensibilidade Microbiana
Extratos Vegetais/química
Folhas de Planta/química
Raízes de Plantas/química
Caules de Planta/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Berberine Alkaloids); 0 (Plant Extracts); 7C782967RD (Ampicillin); R72LW146E6 (Cephalothin)
[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:160114
[St] Status:MEDLINE


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[PMID]:26729496
[Au] Autor:Rojas LJ; Taracila MA; Papp-Wallace KM; Bethel CR; Caselli E; Romagnoli C; Winkler ML; Spellberg B; Prati F; Bonomo RA
[Ad] Endereço:Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA Departments of Medicine, Case Western Reserve University, Cleveland, Ohio, USA Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA.
[Ti] Título:Boronic Acid Transition State Inhibitors Active against KPC and Other Class A ß-Lactamases: Structure-Activity Relationships as a Guide to Inhibitor Design.
[So] Source:Antimicrob Agents Chemother;60(3):1751-9, 2016 Jan 04.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Boronic acid transition state inhibitors (BATSIs) are competitive, reversible ß-lactamase inhibitors (BLIs). In this study, a series of BATSIs with selectively modified regions (R1, R2, and amide group) were strategically designed and tested against representative class A ß-lactamases of Klebsiella pneumoniae, KPC-2 and SHV-1. Firstly, the R1 group of compounds 1a to 1c and 2a to 2e mimicked the side chain of cephalothin, whereas for compounds 3a to 3c, 4a, and 4b, the thiophene ring was replaced by a phenyl, typical of benzylpenicillin. Secondly, variations in the R2 groups which included substituted aryl side chains (compounds 1a, 1b, 1c, 3a, 3b, and 3c) and triazole groups (compounds 2a to 2e) were chosen to mimic the thiazolidine and dihydrothiazine ring of penicillins and cephalosporins, respectively. Thirdly, the amide backbone of the BATSI, which corresponds to the amide at C-6 or C-7 of ß-lactams, was also changed to the following bioisosteric groups: urea (compound 3b), thiourea (compound 3c), and sulfonamide (compounds 4a and 4b). Among the compounds that inhibited KPC-2 and SHV-1 ß-lactamases, nine possessed 50% inhibitory concentrations (IC50s) of ≤ 600 nM. The most active compounds contained the thiopheneacetyl group at R1 and for the chiral BATSIs, a carboxy- or hydroxy-substituted aryl group at R2. The most active sulfonamido derivative, compound 4b, lacked an R2 group. Compound 2b (S02030) was the most active, with acylation rates (k2/K) of 1.2 ± 0.2 × 10(4) M(-1) s(-1) for KPC-2 and 4.7 ± 0.6 × 10(3) M(-1) s(-1) for SHV-1, and demonstrated antimicrobial activity against Escherichia coli DH10B carrying blaSHV variants and blaKPC-2 or blaKPC-3 and against clinical strains of Klebsiella pneumoniae and E. coli producing different class A ß-lactamase genes. At most, MICs decreased from 16 to 0.5 mg/liter.
[Mh] Termos MeSH primário: Ácidos Borônicos/farmacologia
Escherichia coli/efeitos dos fármacos
Klebsiella pneumoniae/efeitos dos fármacos
Triazóis/farmacologia
Inibidores de beta-Lactamases/farmacologia
beta-Lactamases/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ácidos Borônicos/química
Ceftazidima/química
Cefalotina/química
Escherichia coli/genética
Escherichia coli/metabolismo
Klebsiella pneumoniae/genética
Klebsiella pneumoniae/metabolismo
Testes de Sensibilidade Microbiana
Penicilinas/química
Relação Estrutura-Atividade
[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 (Boronic Acids); 0 (Penicillins); 0 (S02030); 0 (Triazoles); 0 (beta-Lactamase Inhibitors); 9M416Z9QNR (Ceftazidime); EC 3.5.2.- (beta-lactamase PIT-2); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase KPC-2, Klebsiella pneumoniae); R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160106
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.02641-15


  8 / 2369 MEDLINE  
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[PMID]:26394804
[Au] Autor:Parker SL; Guerra Valero YC; Roberts DM; Lipman J; Roberts JA; Wallis SC
[Ad] Endereço:Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
[Ti] Título:Determination of Cefalothin and Cefazolin in Human Plasma, Urine and Peritoneal Dialysate by UHPLC-MS/MS: application to a pilot pharmacokinetic study in humans.
[So] Source:Biomed Chromatogr;30(6):872-9, 2016 Jun.
[Is] ISSN:1099-0801
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the analysis of cefazolin and cefalothin in human plasma (total and unbound), urine and peritoneal dialysate has been developed and validated. Total plasma concentrations are measured following protein precipitation and are suitable for the concentration range of 1-500 µg/mL. Unbound concentrations are measured from ultra-filtered plasma acquired using Centrifree(®) devices and are suitable for the concentration range of 0.1-500 µg/mL for cefazolin and 1-500 µg/mL for cefalothin. The urine method is suitable for a concentration range of 0.1-20 mg/mL for cefazolin and 0.2-20 mg/mL for cefalothin. Peritoneal dialysate concentrations are measured using direct injection, and are suitable for the concentration range of 0.2-100 µg/mL for both cefazolin and cefalothin. The cefazolin and cefalothin plasma (total and unbound), urine and peritoneal dialysate results are reported for recovery, inter-assay precision and accuracy, and the lower limit of quantification, linearity, stability and matrix effects, with all results meeting acceptance criteria. The method was used successfully in a pilot pharmacokinetic study with patients with peritoneal dialysis-associated peritonitis, receiving either intraperitoneal cefazolin or cefalothin. Copyright © 2015 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Cefazolina/farmacocinética
Cefalotina/farmacocinética
Cromatografia Líquida de Alta Pressão/métodos
Diálise Peritoneal
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Cefazolina/sangue
Cefazolina/urina
Cefalotina/sangue
Cefalotina/urina
Seres Humanos
Limite de Detecção
Projetos Piloto
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
IHS69L0Y4T (Cefazolin); R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170207
[Lr] Data última revisão:
170207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150924
[St] Status:MEDLINE
[do] DOI:10.1002/bmc.3622


  9 / 2369 MEDLINE  
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[PMID]:27097466
[Au] Autor:Qiu Y; Qin F; Wen H; Zhao J; Liu H; Yang M
[Ti] Título:[Impurity profile study of cefalotin sodium by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry].
[So] Source:Se Pu;33(12):1314-9, 2015 Dec.
[Is] ISSN:1000-8713
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:A two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D-LC-QTOF MS) method to profile the impurities of cefalotin sodium was developed. A Symmetry C18 column (250 mm x 4.6 mm, 5 µm) was used in the first dimensional chromatography, with gradient elution using pH 2.5 phosphate buffer and acetonitrile as the mobile phases. The column temperature was maintained at 40 degrees C with an ultraviolet detection of 220 nm for analysis. An ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 µm) was used in the second dimensional chromatography, with gradient elution using water containing 0.1% (v/v) formic acid and acetonitrile containing 0.1% (v/v) formic acid as the mobile phases. The column temperature was maintained at 40 degrees C. An HLB C18 column (30 mm x 2.1 mm, 20 µm) was used as the trap column. The data were collected in positive ion mode. The ion source temperature was set at 100 degrees C and the electrospray ionization (ESI) needle voltage was set at 1 000 V. The nebulizer gas temperature was set at 500 degrees C. The molecular formulas of the impurities were determined by their exact masses and isotope distributions. And the structures were determined by the protonated molecular ions and the manufacturing process of cefalotin sodium. Six impurities of cefalotin sodium were characterized and the origination of the impurities was deduced. Three of them were unknown impurities to the best of our knowledge. It was confirmed that the Chinese Pharmacopoeia 2010 has mistaken impurity A of cefalotin sodium. The results indicated that the 2D-LC-QTOF MS method could be used to investigate the impurity profile of cefalotin sodium, and it is simple and sensitive.
[Mh] Termos MeSH primário: Cefalotina/análise
Contaminação de Medicamentos
[Mh] Termos MeSH secundário: Cromatografia Líquida
Espectrometria de Massas
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:161018
[Lr] Data última revisão:
161018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160422
[St] Status:MEDLINE


  10 / 2369 MEDLINE  
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[PMID]:26416019
[Au] Autor:Beloglazova NV; Eremin SA
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Laboratory of Food Analysis, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. natalia.beloglazova@ugent.be.
[Ti] Título:Design of a sensitive fluorescent polarization immunoassay for rapid screening of milk for cephalexin.
[So] Source:Anal Bioanal Chem;407(28):8525-32, 2015 Nov.
[Is] ISSN:1618-2650
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In this paper we describe the development of a sensitive, fast, and easily performed fluorescence polarization immunoassay for determination of cephalexin in milk. The experimental work was performed to increase sensitivity and specificity. Therefore, the structures of the tracers were varied by synthesis of both cephalexin (CEX) and cephalotin (CET) conjugates with a variety of fluorescent labels. Two rabbit antisera containing antibodies against cephalexin and cephalotin were tested in homologous and heterologous combinations with the tracers. For every working antibody-tracer combination, the analytical conditions and cross-reactivity for structural analogues-cephalosporins and other antibiotics that could also be present in milk-were determined. It was found that the highest sensitivity was achieved by use of the homologous pair CET-EDF-anti-CET antibody (limit of detection (LOD) 0.4 µg kg(-1) for standard solutions prepared in buffer), but this combination was not appropriate because of high cross-reactivity with CET. For subsequent experiments, therefore, CEX- EDF-anti-CEX antibody were chosen (LOD 0.8 µg kg(-1) for standard solutions prepared in buffer). Part of this manuscript is devoted to the variation of precipitation agents for pretreatment of milk before analysis; milk is an extremely complicated matrix. The optimum protein precipitation agent was methanol. This technique for cephalexin determination was characterized by a limit of detection of 1 µg kg(-1). The method was validated by using naturally contaminated and spiked milk samples. The results obtained corresponded very well with those obtained by HPLC, which was used as confirmation method.
[Mh] Termos MeSH primário: Antibacterianos/análise
Cefalexina/análise
Cefalotina/análise
Resíduos de Drogas/análise
Imunoensaio de Fluorescência por Polarização/métodos
Leite/química
[Mh] Termos MeSH secundário: Animais
Anticorpos/química
Reações Cruzadas
Fluoresceínas/química
Imunoensaio de Fluorescência por Polarização/normas
Corantes Fluorescentes/química
Análise de Alimentos/métodos
Seres Humanos
Imunoconjugados/química
Limite de Detecção
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antibodies); 0 (Fluoresceins); 0 (Fluorescent Dyes); 0 (Immunoconjugates); 75453-82-6 (fluorescein thiocarbamylethylenediamine); OBN7UDS42Y (Cephalexin); R72LW146E6 (Cephalothin)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151106
[Lr] Data última revisão:
151106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150930
[St] Status:MEDLINE
[do] DOI:10.1007/s00216-015-9006-6



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