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Annals of Intensive Care
Published in: Annals of Intensive Care 1/2016

Open Access 01-12-2016 | Research

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

Authors: Nicolas Allou, Astrid Bouteau, Jérôme Allyn, Aurélie Snauwaert, Dorothée Valance, Julien Jabot, Bruno Bouchet, Richard Galliot, Laure Corradi, Philippe Montravers, Pascal Augustin

Published in: Annals of Intensive Care | Issue 1/2016

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Abstract

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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Metadata
Title
Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock
Authors
Nicolas Allou
Astrid Bouteau
Jérôme Allyn
Aurélie Snauwaert
Dorothée Valance
Julien Jabot
Bruno Bouchet
Richard Galliot
Laure Corradi
Philippe Montravers
Pascal Augustin
Publication date
01-12-2016
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2016
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-016-0211-z

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