Determinants of amikacin first peak concentration in critically ill patients

Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (C_max ) to the minimum inhibitory concentration. A target C_max ≥ 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of C_max ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on C_max target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean C_max in the 339 patients was 73.0 ± 23.9 mg/L, with a target attainment rate (TAR, C_max ≥ 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW ≥ 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor of C_max . Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose ≥ 37.8 mg/kg of LBW should be used to optimize the attainment of C_max ≥ 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function.