Introduction

KAVANAGH, FREDERICK

doi:10.1016/b978-0-12-403502-7.50008-9

Cited by 4 publications

(9 citation statements)

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“…The concentrations of phosphomycin in plasma and pleural fluid were determined by a plate diffusion method with Proteus vulgaris MB-838 as the test organism (9). Calibration curves of phosphomycin were prepared in human plasma (concentrations from 200 to 6.25 ,ug/ml) and in human pleural fluid (concentrations from 100 to 6.25 ,ug/ml).…”

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Disposition of phosphomycin in patients with pleural effusion

Lastra¹,

Mariño²,

Barrueco³

et al. 1984

Antimicrob Agents Chemother

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The pharmacokinetics of phosphomycin were studied in seven patients with pleural effusion of varied etiologies. All patients received a single intravenous bolus of 30 mg of antibiotic per kg. Phosphomycin levels in plasma and pleural fluid were determined simultaneously. Antibiotic levels in plasma followed a two-compartment open kinetic model. In the pleural fluid, maximum concentrations of phosphomycin, 42.63 ± 16.03 ,ig/ml (mean ± standard deviation), were reached at 3.69 ± 1.08 h after administration of the antibiotic. The disappearance constant of the antibiotic from the pleural fluid was significantly smaller (0.16 ± 0.06 h-1) than the elimination constant determined from the levels of drug in plasma (0.73 ± 0.26 h-1).Phosphomycin persisted in antibacterial concentrations in the pleural fluid for a considerable period of time. The low accessibility of phosphomycin observed in one of the patients in the study, with a maximum concentration value of 2.16 ,ug of phosphomycin per ml of pleural fluid, could be due to the existence of pachypleuritis in that patient; this was later confirmed in clinical and histological studies done after the research described here.Phosphomycin, (-)-(lR,2S)-(1,2-epoxipropyl)phosphonic acid, is an antibiotic with a molecular weight of 138.1. It is not bound to proteins or biotransformed, and it is principally excreted through the kidney. Several studies have shown its activity against gram-positive and gram-negative organisms (7, 10, 11), and its clinical efficiency in the treatment of infections of the respiratory (2), gastrointestinal (14), and urinogenital (1) tracts has been demonstrated.The determination of the levels reached by antibiotics in pleural fluid is of great interest due to the high number of secondary pleural effusions resulting from pulmonary infections (4, 5). This is, therefore, a determining factor in the treatment of infectious processes localized at this site. The aim of the present study was to establish the accessibility and persistence of an antibiotic such as phosphomycin in pleural fluid in circumstances in which it is necessary to achieve therapeutic concentrations in both pleural fluid and the pulmonary parenchyma, which will result in the eradication of the infectious process.(This work was presented in part at the 13th International Congress of Chemotherapy, Vienna, Austria, 1983.) MATERIALS AND METHODS Patients. The pharmacokinetics of phosphomycin were studied in seven adult patients with pleural effusion, six male and one female, ranging from 54 to 85 years of age. None presented evidence of renal or hepatic pathology. 458Administration of antibiotic and obtaining of samples. All patients received a single intravenous bolus dose of phosphomycin at 30 mg/kg. Antibiotic levels were determined simultaneously in plasma and pleural fluid. Samples of the latter were obtained by catheterization after direct pleural puncture. Samples of blood (treated with heparin) and pleural fluid were obtained at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h after admini...

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mentioning

confidence: 99%

Disposition of phosphomycin in patients with pleural effusion

Lastra¹,

Mariño²,

Barrueco³

et al. 1984

Antimicrob Agents Chemother

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“…quantitativa do composto químico, bem como de um padrão de referência para se determinar uma possível redução na atividade deste antimicrobiano (ESMERINO et al, 2006;GAVIN et al, 1956). Neste tipo de doseamento, a resposta do micro-organismos à amostra é comparada com a resposta à uma preparação padrão, cuja concentração e composição são conhecidas (KAVANAGH, 1972;PINTO et al, 2010). (GAVIN, 1957;KAVANAGH, 1972).…”

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“…O micro-organismo teste usualmente é aquele que pertence às várias estirpes presentes em muitos laboratórios (KAVANAGH, 1972).…”

Section: Incubação E Micro-organismounclassified

“…A temperatura ideal deve ser investigada do ponto de vista de sensibilidade e precisão. O tempo de incubação pode variar sem afetar a potência da amostra, uma incubação prolongada poderá reduzir a inclinação da curva de dose-resposta, contudo, se excessivamente longa, a linha doseresposta pode ser apagada porque o antibiótico reduz a taxa de crescimento do micro-organismo, mas não seu crescimento total (KAVANAGH, 1972).…”

Section: Incubação E Micro-organismounclassified

“…0,4, 0,6, 0,8 e 1 UI/mL, demonstram que a cinética de crescimento da Candida albicans (ATCC 10231), conforme demonstrado no Gráfico 3, é alterada de forma que o antibiótico reduz a velocidade de crescimento do micro-organismo teste. As inclinações da curva de crescimento da Candida albicans (ATCC 10231), na fase log, permitem concluir que em concentrações mais altas de nistatina a velocidade de crescimento microbiano é menor (KAVANAGH, 1972;PINTO et al, 2010;LOURENÇO et al, 2009). !…”

Section: ! Gráfico 1 -Gráfico De Definição De Inóculounclassified

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Doseamento microbiológico de nistatina: desenvolvimento e validação de método empregando leitura cinética em microplaca

Pedroso¹

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Synthesis of cephalosporins carrying isoxazolyl acetamido and related side chains

Sztaricskai

Batta

Dinya

et al. 1998

Chem Heterocycl Compd

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Starting from 3,5-dimethylisoxazole the carboxylic acids I and V, the amino adds VIII CL,-) and IX (D-), and the ureido adds X (L-) and XI (D-) were prepared, which were used for the synthesis of the new cephalosporins XVIIb, XXa--c (L-), and XXIb (D-). The/n v/tro antibacterial activity of these semi-synthetic antibiotics was studied. The resorption of XVIIb was investigated in mice.During the past decades numerous semi-synthetic cephalosporins carrying an alkyl-, alkenyl-, or a heteroarylthioacetamido sidechain have been synthesized [1][2][3][4][5][6][7], and the preparation of oxa-analogues with a related structure has also been reported [4]. Of these semi-synthetic antibiotics only Cefotetan is introduced to medicinal therapy ('Ihble 1). It is surprising, however, that relatively less cephalosporin molecules fuuctionalized with an oxazolyl- [8, 9] or isor, azolyl group [10, 11] at positions 3 or 7 have been prepared, despite the fact that the therapeutic value of similar semi-synthetic penicillins (e.g. Oxacillin, etc.) has been long recognized.To fdl in this gap, the present paper reports our studies on the chemical synthesis and in vitro structure-antibacterial activity relationship of new, diversely substituted isoxazolylacetamido-and thioacetamido cephalosporins. CHEMISTRYThe preparation of 3,5-dimethylisoxazol-4-ylacetic acid (I), suitable for the acylation of the cephalosporin nucleus, was carried out [12] in three steps (Scheme 1) from 3,5-dimethylisoxazole (II), and the product was identical with that reported by March in 1901 [13]. Besides the 1H-NMR data [200 MHz, CDC13, 8 ppm: 2.25 and 2.38 (3H, s, 3-and 5-CH3); 3.38 (2H, s, --CH2--); 8.80 (1H, br, COOH)], the structure of acid I was also supported by transformation into the crystalline 3,5-dimethylisoxazol-4-ylacetic acid N-hydroxysuccinimine ester III in excellent yield, which was then used for the acylation.5-Bromgmethyl-4-chloro-3-methylisoxazole (IV), required for the introduction of various isoxazol-5-ylthioacetamido side chains, was also obtained from II [14]. Treatment of bromide IV with thioglycolic acid in 80% aqueous acetone in the presence of triethylamine (20~ 24 h) readily furnished 5-(carboxymethylthio)methyl-4-chloro-3-methylisoxazole which was isolated in form of the potassium salt V. Oxidation of the latter with hydrogen peroxide in glacial acetic acid afforded 5-(carboxymethylsulfonyl)methyl-4-chloro-3-methylisoxazole (VI).The reaction of IV with L-cysteine (VII; R 2 = R 3 = H) and D-penicillamine (VII; R 2 = R 3 = CH3) was carried out in abs. ethanol in the presence of sodium methoxide (20 ~ 1 h), and the new amino acids VIII (L-) and IX (D-), respectively, were isolated after acidification (pH -5) of the reaction mixture. Treatment of acids VIII and IX with potassium cyanide in refluxing water at pH -2 gave the highly crystalline a-ureido compounds X (L-) and XI (D-), respectively. The reaction of VIII with Boc20 (20~ 2 h) [15] yielded the N-Boc-amino acid XII as a brown syrup, which was used without further purification. ...

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Introduction

Cited by 4 publications

References 3 publications

Disposition of phosphomycin in patients with pleural effusion

Disposition of phosphomycin in patients with pleural effusion

Doseamento microbiológico de nistatina: desenvolvimento e validação de método empregando leitura cinética em microplaca

Synthesis of cephalosporins carrying isoxazolyl acetamido and related side chains

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