author_facet Pea, Federico
Viale, Pierluigi
Cojutti, Piergiorgio
Furlanut, Mario
Pea, Federico
Viale, Pierluigi
Cojutti, Piergiorgio
Furlanut, Mario
author Pea, Federico
Viale, Pierluigi
Cojutti, Piergiorgio
Furlanut, Mario
spellingShingle Pea, Federico
Viale, Pierluigi
Cojutti, Piergiorgio
Furlanut, Mario
Antimicrobial Agents and Chemotherapy
Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
Infectious Diseases
Pharmacology (medical)
Pharmacology
author_sort pea, federico
spelling Pea, Federico Viale, Pierluigi Cojutti, Piergiorgio Furlanut, Mario 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.01291-12 <jats:title>ABSTRACT</jats:title> <jats:p> The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL <jats:sub>Cr</jats:sub> ) estimates for use in daily clinical practice to target the steady-state concentrations ( <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL <jats:sub>m</jats:sub> ) and CL <jats:sub>Cr</jats:sub> was retrospectively assessed in a cohort of critically ill patients (group 1, <jats:italic>n</jats:italic> = 67) to create a formula for dosage calculation to target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> . The performance of this formula was validated in a similar cohort (group 2, <jats:italic>n</jats:italic> = 56) by comparison of the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s. A significant relationship between CL <jats:sub>m</jats:sub> and CL <jats:sub>Cr</jats:sub> was observed in group 1 ( <jats:italic>r</jats:italic> = 0.72, <jats:italic>P</jats:italic> &lt; 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CL <jats:sub>Cr</jats:sub> (ml/min) + 2.85] × target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> × (24/1,000), led to a significant correlation between the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s ( <jats:italic>r</jats:italic> = 0.92, <jats:italic>P</jats:italic> &lt; 0.001). Dosing nomograms based on CL <jats:sub>Cr</jats:sub> were created to target the meropenem <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance. </jats:p> Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach Antimicrobial Agents and Chemotherapy
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series Antimicrobial Agents and Chemotherapy
source_id 49
title Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_unstemmed Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_full Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_fullStr Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_full_unstemmed Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_short Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_sort dosing nomograms for attaining optimum concentrations of meropenem by continuous infusion in critically ill patients with severe gram-negative infections: a pharmacokinetics/pharmacodynamics-based approach
topic Infectious Diseases
Pharmacology (medical)
Pharmacology
url http://dx.doi.org/10.1128/aac.01291-12
publishDate 2012
physical 6343-6348
description <jats:title>ABSTRACT</jats:title> <jats:p> The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL <jats:sub>Cr</jats:sub> ) estimates for use in daily clinical practice to target the steady-state concentrations ( <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL <jats:sub>m</jats:sub> ) and CL <jats:sub>Cr</jats:sub> was retrospectively assessed in a cohort of critically ill patients (group 1, <jats:italic>n</jats:italic> = 67) to create a formula for dosage calculation to target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> . The performance of this formula was validated in a similar cohort (group 2, <jats:italic>n</jats:italic> = 56) by comparison of the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s. A significant relationship between CL <jats:sub>m</jats:sub> and CL <jats:sub>Cr</jats:sub> was observed in group 1 ( <jats:italic>r</jats:italic> = 0.72, <jats:italic>P</jats:italic> &lt; 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CL <jats:sub>Cr</jats:sub> (ml/min) + 2.85] × target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> × (24/1,000), led to a significant correlation between the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s ( <jats:italic>r</jats:italic> = 0.92, <jats:italic>P</jats:italic> &lt; 0.001). Dosing nomograms based on CL <jats:sub>Cr</jats:sub> were created to target the meropenem <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance. </jats:p>
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author Pea, Federico, Viale, Pierluigi, Cojutti, Piergiorgio, Furlanut, Mario
author_facet Pea, Federico, Viale, Pierluigi, Cojutti, Piergiorgio, Furlanut, Mario, Pea, Federico, Viale, Pierluigi, Cojutti, Piergiorgio, Furlanut, Mario
author_sort pea, federico
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description <jats:title>ABSTRACT</jats:title> <jats:p> The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL <jats:sub>Cr</jats:sub> ) estimates for use in daily clinical practice to target the steady-state concentrations ( <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL <jats:sub>m</jats:sub> ) and CL <jats:sub>Cr</jats:sub> was retrospectively assessed in a cohort of critically ill patients (group 1, <jats:italic>n</jats:italic> = 67) to create a formula for dosage calculation to target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> . The performance of this formula was validated in a similar cohort (group 2, <jats:italic>n</jats:italic> = 56) by comparison of the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s. A significant relationship between CL <jats:sub>m</jats:sub> and CL <jats:sub>Cr</jats:sub> was observed in group 1 ( <jats:italic>r</jats:italic> = 0.72, <jats:italic>P</jats:italic> &lt; 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CL <jats:sub>Cr</jats:sub> (ml/min) + 2.85] × target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> × (24/1,000), led to a significant correlation between the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s ( <jats:italic>r</jats:italic> = 0.92, <jats:italic>P</jats:italic> &lt; 0.001). Dosing nomograms based on CL <jats:sub>Cr</jats:sub> were created to target the meropenem <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance. </jats:p>
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spelling Pea, Federico Viale, Pierluigi Cojutti, Piergiorgio Furlanut, Mario 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.01291-12 <jats:title>ABSTRACT</jats:title> <jats:p> The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL <jats:sub>Cr</jats:sub> ) estimates for use in daily clinical practice to target the steady-state concentrations ( <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL <jats:sub>m</jats:sub> ) and CL <jats:sub>Cr</jats:sub> was retrospectively assessed in a cohort of critically ill patients (group 1, <jats:italic>n</jats:italic> = 67) to create a formula for dosage calculation to target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> . The performance of this formula was validated in a similar cohort (group 2, <jats:italic>n</jats:italic> = 56) by comparison of the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s. A significant relationship between CL <jats:sub>m</jats:sub> and CL <jats:sub>Cr</jats:sub> was observed in group 1 ( <jats:italic>r</jats:italic> = 0.72, <jats:italic>P</jats:italic> &lt; 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CL <jats:sub>Cr</jats:sub> (ml/min) + 2.85] × target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> × (24/1,000), led to a significant correlation between the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s ( <jats:italic>r</jats:italic> = 0.92, <jats:italic>P</jats:italic> &lt; 0.001). Dosing nomograms based on CL <jats:sub>Cr</jats:sub> were created to target the meropenem <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance. </jats:p> Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach Antimicrobial Agents and Chemotherapy
spellingShingle Pea, Federico, Viale, Pierluigi, Cojutti, Piergiorgio, Furlanut, Mario, Antimicrobial Agents and Chemotherapy, Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach, Infectious Diseases, Pharmacology (medical), Pharmacology
title Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_full Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_fullStr Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_full_unstemmed Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_short Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
title_sort dosing nomograms for attaining optimum concentrations of meropenem by continuous infusion in critically ill patients with severe gram-negative infections: a pharmacokinetics/pharmacodynamics-based approach
title_unstemmed Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach
topic Infectious Diseases, Pharmacology (medical), Pharmacology
url http://dx.doi.org/10.1128/aac.01291-12