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Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy

INTRODUCTION: Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT co...

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Autores principales: Seyler, Lucie, Cotton, Frédéric, Taccone, Fabio Silvio, De Backer, Daniel, Macours, Pascale, Vincent, Jean-Louis, Jacobs, Frédérique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219006/
https://www.ncbi.nlm.nih.gov/pubmed/21649882
http://dx.doi.org/10.1186/cc10257
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author Seyler, Lucie
Cotton, Frédéric
Taccone, Fabio Silvio
De Backer, Daniel
Macours, Pascale
Vincent, Jean-Louis
Jacobs, Frédérique
author_facet Seyler, Lucie
Cotton, Frédéric
Taccone, Fabio Silvio
De Backer, Daniel
Macours, Pascale
Vincent, Jean-Louis
Jacobs, Frédérique
author_sort Seyler, Lucie
collection PubMed
description INTRODUCTION: Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient populations in which different CRRT devices and techniques have been used. We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT. METHODS: This open, prospective study enrolled consecutive patients treated with CRRT and receiving either meropenem (MEM), piperacillin-tazobactam (TZP), cefepime (FEP) or ceftazidime (CAZ). Serum concentrations of these antibiotics were determined by high-performance liquid chromatography from samples taken before (t = 0) and 1, 2, 5, and 6 or 12 hours (depending on the β-lactam regimen) after the administration of each antibiotic. Series of measurements were separated into those taken during the early phase (< 48 hours from the first dose) of therapy and those taken later (> 48 hours). RESULTS: A total of 69 series of serum samples were obtained in 53 patients (MEM, n = 17; TZP, n = 16; FEP, n = 8; CAZ, n = 12). Serum concentrations remained above four times the minimal inhibitory concentration for Pseudomonas spp. for the recommended time in 81% of patients treated with MEM, in 71% with TZP, in 53% with CAZ and in 0% with FEP. Accumulation after 48 hours of treatment was significant only for MEM. CONCLUSIONS: In septic patients receiving CRRT, recommended doses of β-lactams for Pseudomonas aeruginosa are adequate for MEM but not for TZP, FEP and CAZ; for these latter drugs, higher doses and/or extended infusions should be used to optimise serum concentrations.
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spelling pubmed-32190062011-11-17 Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy Seyler, Lucie Cotton, Frédéric Taccone, Fabio Silvio De Backer, Daniel Macours, Pascale Vincent, Jean-Louis Jacobs, Frédérique Crit Care Research INTRODUCTION: Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient populations in which different CRRT devices and techniques have been used. We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT. METHODS: This open, prospective study enrolled consecutive patients treated with CRRT and receiving either meropenem (MEM), piperacillin-tazobactam (TZP), cefepime (FEP) or ceftazidime (CAZ). Serum concentrations of these antibiotics were determined by high-performance liquid chromatography from samples taken before (t = 0) and 1, 2, 5, and 6 or 12 hours (depending on the β-lactam regimen) after the administration of each antibiotic. Series of measurements were separated into those taken during the early phase (< 48 hours from the first dose) of therapy and those taken later (> 48 hours). RESULTS: A total of 69 series of serum samples were obtained in 53 patients (MEM, n = 17; TZP, n = 16; FEP, n = 8; CAZ, n = 12). Serum concentrations remained above four times the minimal inhibitory concentration for Pseudomonas spp. for the recommended time in 81% of patients treated with MEM, in 71% with TZP, in 53% with CAZ and in 0% with FEP. Accumulation after 48 hours of treatment was significant only for MEM. CONCLUSIONS: In septic patients receiving CRRT, recommended doses of β-lactams for Pseudomonas aeruginosa are adequate for MEM but not for TZP, FEP and CAZ; for these latter drugs, higher doses and/or extended infusions should be used to optimise serum concentrations. BioMed Central 2011 2011-06-06 /pmc/articles/PMC3219006/ /pubmed/21649882 http://dx.doi.org/10.1186/cc10257 Text en Copyright ©2011 Seyler et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Seyler, Lucie
Cotton, Frédéric
Taccone, Fabio Silvio
De Backer, Daniel
Macours, Pascale
Vincent, Jean-Louis
Jacobs, Frédérique
Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
title Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
title_full Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
title_fullStr Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
title_full_unstemmed Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
title_short Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
title_sort recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219006/
https://www.ncbi.nlm.nih.gov/pubmed/21649882
http://dx.doi.org/10.1186/cc10257
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