The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Jeffrey Lipman - One of the best experts on this subject based on the ideXlab platform.
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Continuous Infusion of time-dependent antibiotics: lung pharmacokinetics and pharmacodynamics
Clinical Pulmonary Medicine, 2008Co-Authors: Jason A Roberts, Jennifer Paratz, Elizabeth D. Paratz, Robert J. Boots, Jeffrey LipmanAbstract:Lung infections continue to represent a significant burden to the healthcare system and improved antibiotic therapy may serve as a means to improve patient outcomes. Time-dependent antibiotics such as [beta]-lactams and glycopeptides are commonly used as therapy for lung infections, and the emerging data suggest that administration by Continuous Infusion may result in improved patient outcomes. The aim of this review is to identify and analyze the published literature on lung penetration of time-dependent antibiotics administered by Continuous Infusion. Although only 16 relevant articles were identified during this structured review, data suggest that Continuous Infusion may have an important role in therapy for various lung infections. In acute lung injury, such as pneumonia, where local inflammation causes tight junctions between alveolar membrane epithelial cells to open, antibiotic penetration is significant. Continuous Infusion of time-dependent antibiotics in these patients results in higher trough concentrations than bolus administration that optimizes the pharmacodynamic properties of these antibiotics. In chronic lung injuries, as evidenced in cystic fibrosis and chronic bronchitis, fibrotic scarring and the presence of thick mucus leads to highly variable but significantly reduced antibiotic penetration. In the presence of such pathology, Continuous Infusion of these antibiotics seems to normalize variable pharmacokinetic parameters as well as result in higher trough concentrations compared with bolus administration. Continuous Infusion of time-dependent antibiotics seems to be a suitable method for optimizing antibiotic concentrations at the site of lung infections and as a result may lead to improved treatment success.
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Better outcomes through Continuous Infusion of time-dependent antibiotics to critically ill patients?
Current Opinion in Critical Care, 2008Co-Authors: Jason A Roberts, Jeffrey Lipman, Stijn Blot, Jordi RelloAbstract:PURPOSE OF REVIEW: Increasing interest is being directed toward possible benefits associated with Continuous Infusion of time-dependent antibiotics such as beta-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with Continuous Infusions are discussed. RECENT FINDINGS: One large retrospective cohort study has found clinical outcome benefits of administering a beta-lactam antibiotic by extended Infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing Continuous Infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics. SUMMARY: Continuous Infusion of vancomycin and beta-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for Continuous Infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and Continuous administration of beta-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.
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Continuous Infusion of β lactam antibiotics in severe infections a review of its role
International Journal of Antimicrobial Agents, 2007Co-Authors: Jeffrey Lipman, Jason A Roberts, Jennifer Paratz, Elizabeth D. Paratz, Wolfgang A KruegerAbstract:Abstract Continuous Infusion of β-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of β-lactam antibiotics when administered by Continuous Infusion. This advantage of Continuous Infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is ≥4 mg/L. One drawback of Continuous Infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged Infusions (i.e. >3 h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and Continuous dosing of β-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with Continuous Infusion in seriously ill patients. Pharmacoeconomic advantages of Continuous Infusion of β-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (≥4 days) may be the subgroup that will achieve better outcomes with Continuous Infusion.
Jason A Roberts - One of the best experts on this subject based on the ideXlab platform.
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Continuous Infusion of time-dependent antibiotics: lung pharmacokinetics and pharmacodynamics
Clinical Pulmonary Medicine, 2008Co-Authors: Jason A Roberts, Jennifer Paratz, Elizabeth D. Paratz, Robert J. Boots, Jeffrey LipmanAbstract:Lung infections continue to represent a significant burden to the healthcare system and improved antibiotic therapy may serve as a means to improve patient outcomes. Time-dependent antibiotics such as [beta]-lactams and glycopeptides are commonly used as therapy for lung infections, and the emerging data suggest that administration by Continuous Infusion may result in improved patient outcomes. The aim of this review is to identify and analyze the published literature on lung penetration of time-dependent antibiotics administered by Continuous Infusion. Although only 16 relevant articles were identified during this structured review, data suggest that Continuous Infusion may have an important role in therapy for various lung infections. In acute lung injury, such as pneumonia, where local inflammation causes tight junctions between alveolar membrane epithelial cells to open, antibiotic penetration is significant. Continuous Infusion of time-dependent antibiotics in these patients results in higher trough concentrations than bolus administration that optimizes the pharmacodynamic properties of these antibiotics. In chronic lung injuries, as evidenced in cystic fibrosis and chronic bronchitis, fibrotic scarring and the presence of thick mucus leads to highly variable but significantly reduced antibiotic penetration. In the presence of such pathology, Continuous Infusion of these antibiotics seems to normalize variable pharmacokinetic parameters as well as result in higher trough concentrations compared with bolus administration. Continuous Infusion of time-dependent antibiotics seems to be a suitable method for optimizing antibiotic concentrations at the site of lung infections and as a result may lead to improved treatment success.
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Better outcomes through Continuous Infusion of time-dependent antibiotics to critically ill patients?
Current Opinion in Critical Care, 2008Co-Authors: Jason A Roberts, Jeffrey Lipman, Stijn Blot, Jordi RelloAbstract:PURPOSE OF REVIEW: Increasing interest is being directed toward possible benefits associated with Continuous Infusion of time-dependent antibiotics such as beta-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with Continuous Infusions are discussed. RECENT FINDINGS: One large retrospective cohort study has found clinical outcome benefits of administering a beta-lactam antibiotic by extended Infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing Continuous Infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics. SUMMARY: Continuous Infusion of vancomycin and beta-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for Continuous Infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and Continuous administration of beta-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.
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Continuous Infusion of β lactam antibiotics in severe infections a review of its role
International Journal of Antimicrobial Agents, 2007Co-Authors: Jeffrey Lipman, Jason A Roberts, Jennifer Paratz, Elizabeth D. Paratz, Wolfgang A KruegerAbstract:Abstract Continuous Infusion of β-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of β-lactam antibiotics when administered by Continuous Infusion. This advantage of Continuous Infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is ≥4 mg/L. One drawback of Continuous Infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged Infusions (i.e. >3 h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and Continuous dosing of β-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with Continuous Infusion in seriously ill patients. Pharmacoeconomic advantages of Continuous Infusion of β-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (≥4 days) may be the subgroup that will achieve better outcomes with Continuous Infusion.
Jordi Rello - One of the best experts on this subject based on the ideXlab platform.
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Better outcomes through Continuous Infusion of time-dependent antibiotics to critically ill patients?
Current Opinion in Critical Care, 2008Co-Authors: Jason A Roberts, Jeffrey Lipman, Stijn Blot, Jordi RelloAbstract:PURPOSE OF REVIEW: Increasing interest is being directed toward possible benefits associated with Continuous Infusion of time-dependent antibiotics such as beta-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with Continuous Infusions are discussed. RECENT FINDINGS: One large retrospective cohort study has found clinical outcome benefits of administering a beta-lactam antibiotic by extended Infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing Continuous Infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics. SUMMARY: Continuous Infusion of vancomycin and beta-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for Continuous Infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and Continuous administration of beta-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.
Mohammad Reza Fazeli - One of the best experts on this subject based on the ideXlab platform.
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Clinical efficacy of Continuous Infusion of piperacillin compared with intermittent dosing in septic critically ill patients
International Journal of Antimicrobial Agents, 2006Co-Authors: Mohammad Reza Rafati, Mojtaba Mojtahedzadeh, Atabak Najafi, Mohammad Reza Rouini, Hossein Tavakoli, Kheirollah Gholami, Mohammad Reza FazeliAbstract:Since the bactericidal effects of β-lactam antibiotics are time dependent, the optimum strategy for their administration could be Continuous Infusion. In this prospective, randomised controlled trial to evaluate the clinical efficacy of Continuous Infusion therapy, we evaluated the outcomes for 40 septic critically ill patients who received piperacillin either Continuously (2 g intravenously (i.v.) over 0.5 h as a loading dose followed by 8 g i.v. daily over 24 h (n = 20)) or as an intermittent Infusion (3 g i.v. every 6 h over 0.5 h (n = 20)). Results from our study demonstrated that the clinical efficacy of piperacillin as a Continuous Infusion is superior to intermittent administration in critically ill patients. Change in APACHE II scores from baseline at the end of the second, third and fourth days, respectively, were 4.1, 5.1 and 5.2 for Continuous Infusion and 2.0, 2.6 and 2.8 for intermittent Infusion (P ≤ 0.04). Considering minimum inhibitory concentrations (MICs) of 16 μg/mL and 32 μg/mL, the percentage of time for which piperacillin plasma concentrations were higher than the MIC (%T > MIC) was calculated for each patient in the two groups. For MICs of 16 μg/mL and 32 μg/mL, %T > MIC in the Continuous Infusion group was 100% and 65% of the dosing interval, respectively; in the intermittent Infusion group, %T > MIC was only 62% and 39% of the dosing interval. There was a significant relationship between clinical results and laboratory data. It was shown that the superiority of the clinical efficacy of Continuous Infusion could be related to piperacillin pharmacodynamics. Continuous Infusion significantly reduced the severity of illness as demonstrated by APACHE II scores during therapy. © 2006 Elsevier B.V. and the International Society of Chemotherapy.
Luís Bento - One of the best experts on this subject based on the ideXlab platform.
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Continuous Infusion of Piperacillin/Tazobactam in Septic Critically Ill Patients-A Multicenter Propensity Matched Analysis
PLoS ONE, 2012Co-Authors: João Gonçalves-pereira, Bruno Serra Oliveira, Sérgio Janeiro, Joana Estilita, Andrea Salgueiro, Alfredo Vieira, Catarina Monteiro, Joao Gouveia, Carolina Paulino, Luís BentoAbstract:The clinical efficacy of Continuous Infusion of piperacillin/tazobactam in critically ill patients with microbiologically documented infections is currently unknown. We conducted a retrospective multicenter cohort study in 7 Portuguese intensive care units (ICU). We included 569 critically ill adult patients with a documented infection and treated with piperacillin/tazobactam admitted to one of the participating ICU between 2006 and 2010. We successfully matched 173 pairs of patients according to whether they received Continuous or conventional intermittent dosing of piperacillin/tazobactam, using a propensity score to adjust for confounding variables. The majority of patients received 16g/day of piperacillin plus 2g/day of tazobactam. The 28-day mortality rate was 28.3% in both groups (p = 1.0). The ICU and in-hospital mortality were also similar either in those receiving Continuous Infusion or intermittent dosing (23.7% vs. 20.2%, p = 0.512 and 41.6% vs. 40.5%, p = 0.913, respectively). In the subgroup of patients with a Simplified Acute Physiology Score (SAPS) II>42, the 28-day mortality rate was lower in the Continuous Infusion group (31.4% vs. 35.2%) although not reaching significance (p = 0.66). We concluded that the clinical efficacy of piperacillin/tazobactam in this heterogeneous group of critically ill patients infected with susceptible bacteria was independent of its mode of administration, either Continuous Infusion or intermittent dosing.