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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Paris
2016
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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. |
format | Online Article Text |
id | pubmed-5093100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Paris |
record_format | MEDLINE/PubMed |
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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