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Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock

BACKGROUND: The therapeutic effect of aminoglycosides is highest and optimal when the peak plasma concentration (C (max))/minimal inhibitory concentration (MIC) ratio is between 8 and 10. The French guidelines recommend to use high doses of aminoglycosides for empiric antibiotic therapy in patients...

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Autores principales: Allou, Nicolas, Bouteau, Astrid, Allyn, Jérôme, Snauwaert, Aurélie, Valance, Dorothée, Jabot, Julien, Bouchet, Bruno, Galliot, Richard, Corradi, Laure, Montravers, Philippe, Augustin, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Paris 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093100/
https://www.ncbi.nlm.nih.gov/pubmed/27807818
http://dx.doi.org/10.1186/s13613-016-0211-z
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author Allou, Nicolas
Bouteau, Astrid
Allyn, Jérôme
Snauwaert, Aurélie
Valance, Dorothée
Jabot, Julien
Bouchet, Bruno
Galliot, Richard
Corradi, Laure
Montravers, Philippe
Augustin, Pascal
author_facet Allou, Nicolas
Bouteau, Astrid
Allyn, Jérôme
Snauwaert, Aurélie
Valance, Dorothée
Jabot, Julien
Bouchet, Bruno
Galliot, Richard
Corradi, Laure
Montravers, Philippe
Augustin, Pascal
author_sort Allou, Nicolas
collection PubMed
description BACKGROUND: The therapeutic effect of aminoglycosides is highest and optimal when the peak plasma concentration (C (max))/minimal inhibitory concentration (MIC) ratio is between 8 and 10. The French guidelines recommend to use high doses of aminoglycosides for empiric antibiotic therapy in patients suffering from severe sepsis or septic shock. In clinical practice, the recommended target is an amikacin C (max) between 60 and 80 mg/L, which corresponds to approximately 8 times the MIC breakpoint, as defined by the European Committee on Antimicrobial Susceptibility Testing. The aim of this study was to assess the incidence and impact on mortality of an amikacin concentration between 60 and 80 mg/L in patients suffering from severe sepsis or septic shock. METHODS: This was a prospective observational cohort study conducted in two intensive care units (ICU). Patients receiving amikacin at a loading dose of 30 mg/kg for severe sepsis or septic shock were enrolled in the cohort. The target C (max) for amikacin was between 60 and 80 mg/L, as recommended by French guidelines (i.e. C (max)/MIC breakpoint = 8–10). RESULTS: Over the study period, the amikacin C (max) was <60 mg/L, between 60 and 80 mg/L, and >80 mg/L in 20 (18.2%), 46 (41.8%) and 44 (40%) of the 110 selected patients, respectively. Mortality rate was 40, 28.3 and 56.8% in the groups of patients with C (max) < 60 mg/L, 60 mg/L < C (max) < 80 mg/L and C (max) > 80 mg/L, respectively. Following multivariate analysis, mortality rate was significantly lower in the group of patients with amikacin C (max) between 60 and 80 mg/L than in the group of patients with amikacin C (max) > 80 mg/L (P = 0.004). The multivariate analysis also revealed that the factors independently associated with a higher in-ICU mortality rate were age (P = 0.02) and norepinephrine dose (P = 0.0001). CONCLUSIONS: With a loading dose of 30 mg/kg of amikacin, concentration was potentially suboptimal (C (max) < 60 mg/L) in only 18.2% of patients. The pharmacodynamic target (60 mg/L < C (max) < 80 mg/L) recommended by French guidelines was reached in 41.8% of patients and was associated with reduced in-ICU mortality. But amikacin overexposure (i.e. C (max) > 80 mg/L) was frequent and potentially associated with increased mortality.
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spelling pubmed-50931002016-11-18 Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock Allou, Nicolas Bouteau, Astrid Allyn, Jérôme Snauwaert, Aurélie Valance, Dorothée Jabot, Julien Bouchet, Bruno Galliot, Richard Corradi, Laure Montravers, Philippe Augustin, Pascal Ann Intensive Care Research BACKGROUND: The therapeutic effect of aminoglycosides is highest and optimal when the peak plasma concentration (C (max))/minimal inhibitory concentration (MIC) ratio is between 8 and 10. The French guidelines recommend to use high doses of aminoglycosides for empiric antibiotic therapy in patients suffering from severe sepsis or septic shock. In clinical practice, the recommended target is an amikacin C (max) between 60 and 80 mg/L, which corresponds to approximately 8 times the MIC breakpoint, as defined by the European Committee on Antimicrobial Susceptibility Testing. The aim of this study was to assess the incidence and impact on mortality of an amikacin concentration between 60 and 80 mg/L in patients suffering from severe sepsis or septic shock. METHODS: This was a prospective observational cohort study conducted in two intensive care units (ICU). Patients receiving amikacin at a loading dose of 30 mg/kg for severe sepsis or septic shock were enrolled in the cohort. The target C (max) for amikacin was between 60 and 80 mg/L, as recommended by French guidelines (i.e. C (max)/MIC breakpoint = 8–10). RESULTS: Over the study period, the amikacin C (max) was <60 mg/L, between 60 and 80 mg/L, and >80 mg/L in 20 (18.2%), 46 (41.8%) and 44 (40%) of the 110 selected patients, respectively. Mortality rate was 40, 28.3 and 56.8% in the groups of patients with C (max) < 60 mg/L, 60 mg/L < C (max) < 80 mg/L and C (max) > 80 mg/L, respectively. Following multivariate analysis, mortality rate was significantly lower in the group of patients with amikacin C (max) between 60 and 80 mg/L than in the group of patients with amikacin C (max) > 80 mg/L (P = 0.004). The multivariate analysis also revealed that the factors independently associated with a higher in-ICU mortality rate were age (P = 0.02) and norepinephrine dose (P = 0.0001). CONCLUSIONS: With a loading dose of 30 mg/kg of amikacin, concentration was potentially suboptimal (C (max) < 60 mg/L) in only 18.2% of patients. The pharmacodynamic target (60 mg/L < C (max) < 80 mg/L) recommended by French guidelines was reached in 41.8% of patients and was associated with reduced in-ICU mortality. But amikacin overexposure (i.e. C (max) > 80 mg/L) was frequent and potentially associated with increased mortality. Springer Paris 2016-11-02 /pmc/articles/PMC5093100/ /pubmed/27807818 http://dx.doi.org/10.1186/s13613-016-0211-z Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research
Allou, Nicolas
Bouteau, Astrid
Allyn, Jérôme
Snauwaert, Aurélie
Valance, Dorothée
Jabot, Julien
Bouchet, Bruno
Galliot, Richard
Corradi, Laure
Montravers, Philippe
Augustin, Pascal
Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
title Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
title_full Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
title_fullStr Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
title_full_unstemmed Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
title_short Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
title_sort impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093100/
https://www.ncbi.nlm.nih.gov/pubmed/27807818
http://dx.doi.org/10.1186/s13613-016-0211-z
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