Higher versus standard amikacin single dose in emergency department patients with severe sepsis and shock: a randomized controlled trial.

Research paper by Sabrina S De Winter, Joost J Wauters, Wouter W Meersseman, Jan J Verhaegen, Eric E Van Wijngaerden, Willy W Peetermans, Pieter P Annaert, Sandra S Verelst, Isabel I Spriet

Indexed on: 29 Nov '17Published on: 29 Nov '17Published in: International Journal of Antimicrobial Agents


Recent studies suggest that ICU patients treated with amikacin frequently do not attain the PK/PD target, i.e. a peak above minimal inhibitory concentration (MIC) ratio of at least 8, when a single dose of 15 mg/kg is used. No data are available for patients admitted to the emergency department (ED). The aim of this study was to determine PK/PD target attainment in patients presenting with severe sepsis or septic shock and treated with 15 vs. 25 mg/kg of amikacin.This prospective randomized controlled study was undertaken in ED patients admitted with severe sepsis or septic shock. Patients were randomly treated with 25 vs. 15 mg/kg. Amikacin peak concentrations were collected. Primary outcome was target attainment defined as peak/MIC ≥ 8, using both EUCAST susceptibility breakpoints and actually documented MIC values as denominator.104 patients were included. The EUCAST based target was attained in 76% vs. 40% of patients assigned to the 25 vs. 15 mg/kg dose group (p<0.0001). Target attainment using actual MIC values (median of 2 mg/L, documented in 48 isolated gram-negative pathogens) was achieved in 95% vs. 94% of patients in the 25 vs. 15mg/kg group (p=0.969). Risk factors associated with PK/PD target failure were identified in the multivariable analysis.At least 25mg/kg amikacin as a single dose should be used in ED patients with severe sepsis and septic shock to attain the EUCAST based target. However, when using local epidemiology as denominator, 15 mg/kg seems to be sufficient.

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