Pharmacodynamic study of  -lactams alone and in combination with  -lactamase inhibitors against Pseudomonas aeruginosa possessing an inducible  -lactamase

Li, Chonghua; Nicolau, David P.; Lister, Philip; Quintiliani, Richard; Nightingale, Charles H.

doi:10.1093/jac/dkh057

Cited by 19 publications

(15 citation statements)

References 17 publications

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“…Blood samples were centrifuged and separated, and then serum samples were frozen at −80°C prior to assay. TCF samples (400 µL) were aspirated percutaneously at 0, 1, 2, 4, 6, 8 and 12 h, and stored at −80°C without processing (Li et al, 2004).…”

Section: Cross-validation Of the Proxy Matrix Of Rabbit Tcfmentioning

confidence: 99%

Simultaneous analysis of piperacillin and tazobactam in rabbits: application to pharmacokinetic study

Xuan

et al. 2005

Biomed. Chromatogr.

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A simple and rapid assay is developed for the simultaneous analysis of piperacillin and tazobactam in rabbit serum and tissue cage fluid (TCF). To eliminate endogenous interferences, a wavelength switch technique was applied, in which the programmable UV detector changed the monitoring wavelength from 218 to 254 nm at 10 min. After liquid-liquid extraction, sample analyses were performed on a C(18) column by gradient elution; the mobile phase consisted of acetonitrile and phosphate buffer (0.014 m, pH 2.4). Owing to the limited amount of rabbit TCF available, a cross-validation of a proxy matrix was evaluated. The relative standard deviation of the between- and within-batch precision of both compounds was less than 5.1%; the relative error of the between- and within-batch accuracy was less than 7.3%. The recoveries of both compounds in serum and TCF were larger than 80%. This assay was successfully applied to simultaneously analyze piperacillin and tazobactam in rabbit serum and TCF samples.

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Section: Cross-validation Of the Proxy Matrix Of Rabbit Tcfmentioning

confidence: 99%

Simultaneous analysis of piperacillin and tazobactam in rabbits: application to pharmacokinetic study

Xuan

et al. 2005

Biomed. Chromatogr.

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“…The mortality rate is higher than bacteremias caused by other gram-negative opportunistic pathogens. One of the most important features of the bacterium is its resistance to various antibacterial agents [2,3], and even newly developed antibiotics have failed to reduce the mortality rate associated with this organism [4]. …”

Section: Introductionmentioning

confidence: 99%

Active immunization using exotoxin A confers protection against Pseudomonas aeruginosainfection in a mouse burn model

et al. 2009

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BackgroundPseudomonas aeruginosa is an important cause of nosocomial infection and may lead to septicemia and death. We evaluated the immunogenicity of semi-purified exotoxin A from the bacterium in a mouse burn model.MethodsThe toxoid was prepared from exotoxin A taken from toxigenic strains of P. aeruginosa (PA 103). 50 mice were immunized with the toxoid, burned with hot metal and infected with 1 × 108 CFU of toxigenic strains of P. aeruginosa (experimental group); 25 non-immunized mice were also burned and infected (control group). The mortality rate and presence of any exotoxin and P. aeruginosa in the sera, liver and spleen were determined.ResultsIn the experimental group, 2 mice died before the burns were administered and were excluded from the study. The remainder (48 mice) were challenged with a lethal dose of P. aeruginosa and followed for 70 days. 3 of these mice died. Neither P. aeruginosa nor exotoxin A was not detected in the liver, spleen or sera of the surviving mice. The protective efficacy of toxoid vaccination was therefore 93.8%. In the control group, all mice died from bacteremia and septicemia, most (80%) within 6 days, and P. aeruginosa and exotoxin A were isolated from sera, spleen and liver.ConclusionActive immunization of mice using a semi-purified exotoxin A derived from P. aeruginosa was 93.8% effective at protecting mice from subsequent P. aeruginosa infections in a mouse burn model.

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“…More precisely, 4.5 g of drug powder (4 g piperacillin and 0.5 g tazobactam) were reconstituted with 20 ml of the supplied diluent; volume corresponding to the individual dose of each rabbit was further diluted with natural saline to a final volume of 30 ml and was administered intravenously over 30 min. It is anticipated that this regimen corresponds to one intravenous dose of 4.5 g in humans . Group D (n = 10), animals administered both clarithromycin and piperacillin/tazobactam as described for groups B and C.…”

Section: Animals and Methodsmentioning

confidence: 99%

Effect of clarithromycin in experimental empyema by multidrug‐resistant Pseudomonas aeruginosa

Tsovolou

Tzepi

Spyridaki

et al. 2013

APMIS

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Evidence from a recent randomized study of our group suggests that intravenous clarithromycin resulted in earlier resolution of ventilator-associated pneumonia. The need to understand the mechanism of action of clarithromycin guided to the study of a model of experimental empyema by multidrug-resistant Pseudomonas aeruginosa in 40 rabbits. Animals were randomized into controls (group A); treatment with clarithromycin (group B); treatment with piperacillin/tazobactam (group C); and treatment with both agents (group D). Pleural fluid was collected at regular time intervals for quantitative culture, estimation of cell apoptosis and of concentrations of tumour necrosis factor-alpha (TNFα). After 7 days, animals were euthanized for estimation of tissue growth. Bacterial growth in the pleural fluid of group D was significantly decreased compared with the other groups on day 5. Lung growth of group D was lower than group A. That was also the case of cytokine stimulation by pleural fluid samples on U937 monocytes. It is concluded that administration of clarithromycin enhanced the antimicrobial efficacy of piperacillin/tazobactam and decreased bacterial growth in the pleural fluid and in tissues. It also attenuated the pro-inflammatory phenomena induced by the β-lactam.

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Pharmacodynamic study of -lactams alone and in combination with -lactamase inhibitors against Pseudomonas aeruginosa possessing an inducible -lactamase

Cited by 19 publications

References 17 publications

Simultaneous analysis of piperacillin and tazobactam in rabbits: application to pharmacokinetic study

Simultaneous analysis of piperacillin and tazobactam in rabbits: application to pharmacokinetic study

Active immunization using exotoxin A confers protection against Pseudomonas aeruginosainfection in a mouse burn model

Effect of clarithromycin in experimental empyema by multidrug‐resistant Pseudomonas aeruginosa

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