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Article Dans Une Revue International Journal of Antimicrobial Agents Année : 2011

Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy

Résumé

Data on the optimal amikacin regimen during continuous renal replacement therapy (CRRT) are scarce and the proposed loading dose of 10mg/kg may result in inadequate drug levels. The aim of this study was to describe the pharmacokinetics of a 25mg/kg first dose of amikacin in septic shock patients treated with CRRT. Serum samples were collected before (=0h) and at 1 (peak), 1.5, 4.5, 8 and 24h after a 30-min amikacin infusion in 13 consecutive patients treated with a combination of amikacin and β-lactam. Blood amikacin levels were measured using a validated fluorescence polarisation immunoassay method. In 9 patients (69%) the peak concentration was >64mg/L, which corresponds to eight times the minimal inhibitory concentration breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for Enterobacteriaceae and (susceptible <8mg/L, resistant >16mg/L). The median (range) total volume of distribution was 0.50 L/Kg (0.22-4.05L/Kg), the elimination half-life was 6.5h (4.5-279.6h) and total drug clearance (CL) was 1.26mL/min/kg (0.1-3.30mL/min/kg). Only three patients had drug concentrations at 24h () of <5mg/L and the median predicted time needed to reach this value was 34h (14-76h). There was no correlation between CRRT parameters and , CL or the time to <5mg/L. In septic shock patients treated with CRRT, a first dose of ≥25mg/kg amikacin is therefore required to reach therapeutic peak concentrations. However, as drug clearance is reduced, amikacin concentrations remained above the threshold of renal toxicity at 24h. The therapeutic benefit of high-dose aminoglycoside therapy should be balanced with its potential renal effects in septic patients receiving CRRT.
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Dates et versions

hal-00690059 , version 1 (21-04-2012)

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Fabio Silvio Taccone, Daniel de Backer, Pierre-François Laterre, Herbert Spapen, Thierry Dugernier, et al.. Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy. International Journal of Antimicrobial Agents, 2011, ⟨10.1016/j.ijantimicag.2011.01.026⟩. ⟨hal-00690059⟩

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