Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations

• In 90 patients given amikacin (n = 66) or gentamicin (n = 24), an adequate first peak plasma concentration (Cmax) was reached in 17 patients (19%) [16 (24%) for amikacin and 1 (4%) for gentamicin].
• Only aminoglycoside dosing was associated with an adequate or inadequate first Cmax.
• For subsequent doses, an adequate amikacin Cmax was reached in 6/27, 3/33, 1/19 and 4/10 patients, respectively.
• For subsequent doses, an adequate gentamicin Cmax was never reached despite an increase in dosing in 13 patients.

Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in intensive care unit (ICU) patients after administration of the first dose. The present study aimed to describe the proportion of ICU patients in whom an adequate Cmax was achieved throughout the course of therapy. Septic ICU patients with an indication for intravenous amikacin or gentamicin were eligible for inclusion in this single-centre observational study. The first and subsequent doses and the corresponding Cmax values were recorded. The target Cmax was ≥60 mg/L for amikacin and ≥30 mg/L for gentamicin. Amikacin and gentamicin plasma concentrations were available in 66 and 24 patients, respectively (59 ± 17 years; 79 ± 19 kg; height 169 ± 12 cm; SAPS II score 46 ± 19). Pulmonary, abdominal and urinary tract infections were diagnosed in 64 patients. Culture-positive infection was confirmed in 65 patients (72%). A target first Cmax was achieved in 17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66 patients (24%) after the initial dose. In the 50 remaining patients, a change in dosing was performed in 14 patients, leading adequate peak plasma level in 2 patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient (4%) after the initial dose and was never achieved after the third dose. In conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in only 19% of patients. Subtherapeutic Cmax were not significantly corrected after subsequent doses.