Influence of sepsis on higher daily dose of amikacin pharmacokinetics in critically ill patients.

BACKGROUND AND OBJECTIVES Severe sepsis is a major problem as cause of high rates morbidity and mortality in intensive care units (ICU). Aminoglycosides are an important group of antimicrobials used for severe sepsis. However, aminoglycoside pharmacokinetics in ICU patients may be altered during sepsis, which can affect the drug concentrations. Therefore, this study was undertaken to examine the relationship between amikacin disposition kinetics after a 25 mg/kg loading dose and hemodynamic response to sepsis, as well as clinical parameters, in a population of critically ill patients. METHODS In this work, 30 patients who were candidate to amikacin therapy following Gram negative sepsis were enrolled. The pharmacokinetic profile of amikacin by a non-compartmental model was calculated for each patient. RESULTS Mean volume of distribution was 0.36 ± 0.07 L/kg and mean serum amikacin clearance was 3.88 ± 0.97 ml/min/kg. In the case of Vd, APACHE II score correlation was significant. In the case of amikacin clearance, two covariates including creatinine clearance and Sr Cr significant correlation was found. CONCLUSIONS It appears necessary to use higher amikacin dosage (≥ 25 mg/kg) considering hemodynamic response of patients to sepsis. To achieve therapeutic drug concentration a close drug monitoring and a shift from the population mean toward a value more representative of the critically ill patient subpopulation is crucial.