High-dose amikacin for achieving serum target levels in critically ill elderly patients

Kourosh Sadeghi,1 Hadi Hamishehkar,2 Farhad Najmeddin,1 Arezoo Ahmadi,3 Ebrahim Hazrati,4 Hooshyar Honarmand,1 Mojtaba Mojtahedzadeh1,5 1Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Clinical Pharmacy, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 3Department of Anesthesia and Intensive Care, Sina Hospital, Tehran University of Medical Science, Tehran, Iran; 4Department of Anesthesia and Intensive Care, Imam Reza Hospital, Army University of Medical Sciences, Tehran, Iran; 5Pharmaceutical Sciences Research Center, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Introduction: To achieve target concentrations, the application of higher-than-standard doses of amikacin is proposed for the treatment of sepsis due to an increase in volume of distribution and clearance, but little data are available on aminoglycoside administration in critically ill elderly patients. Patients and methods: Forty critically ill elderly patients (aged over 65 years) who required amikacin therapy due to severe documented, or suspected gram-negative infections, were randomly assigned to two treatment groups. Group A (20 patients) received 15 mg/kg amikacin and Group B (20 patients) received 25 mg/kg amikacin per day as a single daily dose. All the patients were monitored for renal damage by the daily monitoring of serum creatinine. The amikacin peak (Cmax) and trough (Cmin) serum concentrations were measured on Days 3 and 7 postadministration. Results: Data from 18 patients in Group A and 15 patients in Group B were finally analyzed. On Day 3, the amikacin mean Cmax levels in the standard and high-dose treatment groups were 30.4±11 and 52.3±16.1 µg/mL (P<0.001), and the Cmin levels were 3.2±2.1 and 5.2±2.8 µg/mL, respectively (P=0.035). On Day 7, the Cmax levels in the standard and high-dose groups were 33±7.3 and 60.0±17.6 µg/mL (P=0.001), and the Cmin levels were 3.2±2.9 and 9.3±5.6 µg/mL, respectively (P=0.002). In only six (40%) of the patients in the high-dose groups and none of the patients in the standard-dose group, amikacin Cmax reached the target levels (>64 µg/mL), whereas the amikacin mean Cmin levels in the high-dose group were above the threshold of toxicity (5 µg/mL). Conclusion: Our results suggest that the optimum dose of amikacin should be determined for elderly critically ill patients. It seems that higher-than-standard doses of amikacin with more extended intervals might be more appropriate than standard once-daily dosing in the elderly critically ill patients. Keywords: amikacin, elderly, high-dose, critical illness, pharmacokinetics, therapeutic drug monitorin