Evaluation of therapeutic goal achievements with once daily usual and high dosing of amikacin in elderly critically ill patients

Abstract

Introduction: Septic shock is the main reason of high rates morbidity and mortality in intensive care unit (ICU). One of the most important groups in antibiotic therapy of severe sepsis, are aminoglycoside. Of which, amikacin has an excellent drug profile, with bactericidal activity against hospital acquired pathogens. The optimum pharmacodynamic target for aminoglycosides is peak serum concentration 8-10 times greater than the minimum inhibitory concentration (MIC). We considered amikacin pharmacokinetic variability in elderly critically ill patients (age˃65). Aim: we aimed to determine pharmacokinetic parameters of amikacin and higher than standard doses of this antibiotic in elderly critically ill patients. Method: This was an open, prospective randomized multi-centered study, performed in two general ICU. Thirty critically ill elderly patients (age ≥ 65, baseline serum creatinine ≤ 1.2 mg/dl) who required amikacin for treatment of severe sepsis were randomized into groups A and B. Patients in group A received 15 mg/kg/day of amikacin and group B were administered with 25 mg/kg/day of this antibiotic. To extend our data beyond a limited group of patients, we used Monte Carlo simulation and evaluated the results in this assumed population. Result: As a primary outcome, no patient in group A and only 50% of the patients in group B reached target peak levels (>60 μg/ml). On the other hand, 5 patients in group A (27.7%) and 13 patients (86.6%) in group B had at least one trough level above 5 μg/ml. No patient in group A and 6 patients (40%) in group B had at least one trough levels above 10 μg/ml. Conclusion: Monte Carlo simulation results revealed that, due to pharmacokinetic alterations in elderly critically ill patients, high doses of amikacin were effective in some patients, however the risk of drug accumulation may increase