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Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance

OBJECTIVES: Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to...

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Autores principales: Chauzy, Alexia, Gregoire, Nicolas, Ferrandière, Martine, Lasocki, Sigismond, Ashenoune, Karim, Seguin, Philippe, Boisson, Matthieu, Couet, William, Marchand, Sandrine, Mimoz, Olivier, Dahyot-Fizelier, Claire
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616540/
https://www.ncbi.nlm.nih.gov/pubmed/36059138
http://dx.doi.org/10.1093/jac/dkac299
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author Chauzy, Alexia
Gregoire, Nicolas
Ferrandière, Martine
Lasocki, Sigismond
Ashenoune, Karim
Seguin, Philippe
Boisson, Matthieu
Couet, William
Marchand, Sandrine
Mimoz, Olivier
Dahyot-Fizelier, Claire
author_facet Chauzy, Alexia
Gregoire, Nicolas
Ferrandière, Martine
Lasocki, Sigismond
Ashenoune, Karim
Seguin, Philippe
Boisson, Matthieu
Couet, William
Marchand, Sandrine
Mimoz, Olivier
Dahyot-Fizelier, Claire
author_sort Chauzy, Alexia
collection PubMed
description OBJECTIVES: Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to explore the impact of ARC on ceftaroline pharmacokinetics and evaluate whether the currently recommended dosing regimen (600 mg every 12 h) is appropriate to treat VAP in ICU patients. METHODS: A population pharmacokinetic model was developed using pharmacokinetic data from 18 patients with measured creatinine clearance (CL(CR)) ranging between 83 and 309 mL/min. Monte Carlo simulations were conducted to determine the PTA and the cumulative fraction of response (CFR) against Streptococcus pneumoniae and MRSA for five dosing regimens. Study registered at ClinicalTrials.gov (NCT03025841). RESULTS: Ceftaroline clearance increased non-linearly with CL(CR), with lower concentrations and lower probability of reaching pharmacokinetic/pharmacodynamic targets when CL(CR) increases. For the currently recommended dosing regimen, the probability of having unbound ceftaroline concentrations above the MIC over the entire dose range is greater than 90% for MICs below 0.125 mg/L. Considering the distribution of MICs, this regimen would not be effective against MRSA infections (CFR between 21% and 67% depending on CL(CR)), but would be effective against S. pneumoniae infections (CFR >86%). CONCLUSIONS: The recommended dosing regimen of ceftaroline seems sufficient for covering S. pneumoniae in ICU patients with ARC, but not for MRSA. Among the dosing regimens tested it appears that a constant infusion (50 mg/h) after a loading dose of 600 mg could be more appropriate for MRSA infections.
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spelling pubmed-96165402022-11-01 Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance Chauzy, Alexia Gregoire, Nicolas Ferrandière, Martine Lasocki, Sigismond Ashenoune, Karim Seguin, Philippe Boisson, Matthieu Couet, William Marchand, Sandrine Mimoz, Olivier Dahyot-Fizelier, Claire J Antimicrob Chemother Original Research OBJECTIVES: Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to explore the impact of ARC on ceftaroline pharmacokinetics and evaluate whether the currently recommended dosing regimen (600 mg every 12 h) is appropriate to treat VAP in ICU patients. METHODS: A population pharmacokinetic model was developed using pharmacokinetic data from 18 patients with measured creatinine clearance (CL(CR)) ranging between 83 and 309 mL/min. Monte Carlo simulations were conducted to determine the PTA and the cumulative fraction of response (CFR) against Streptococcus pneumoniae and MRSA for five dosing regimens. Study registered at ClinicalTrials.gov (NCT03025841). RESULTS: Ceftaroline clearance increased non-linearly with CL(CR), with lower concentrations and lower probability of reaching pharmacokinetic/pharmacodynamic targets when CL(CR) increases. For the currently recommended dosing regimen, the probability of having unbound ceftaroline concentrations above the MIC over the entire dose range is greater than 90% for MICs below 0.125 mg/L. Considering the distribution of MICs, this regimen would not be effective against MRSA infections (CFR between 21% and 67% depending on CL(CR)), but would be effective against S. pneumoniae infections (CFR >86%). CONCLUSIONS: The recommended dosing regimen of ceftaroline seems sufficient for covering S. pneumoniae in ICU patients with ARC, but not for MRSA. Among the dosing regimens tested it appears that a constant infusion (50 mg/h) after a loading dose of 600 mg could be more appropriate for MRSA infections. Oxford University Press 2022-09-05 /pmc/articles/PMC9616540/ /pubmed/36059138 http://dx.doi.org/10.1093/jac/dkac299 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Chauzy, Alexia
Gregoire, Nicolas
Ferrandière, Martine
Lasocki, Sigismond
Ashenoune, Karim
Seguin, Philippe
Boisson, Matthieu
Couet, William
Marchand, Sandrine
Mimoz, Olivier
Dahyot-Fizelier, Claire
Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance
title Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance
title_full Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance
title_fullStr Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance
title_full_unstemmed Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance
title_short Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance
title_sort population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616540/
https://www.ncbi.nlm.nih.gov/pubmed/36059138
http://dx.doi.org/10.1093/jac/dkac299
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