Optimal dose of amikacin in childhood chemotherapy-induced febrile neutropenia: beware of underdosing.

Background and objective. Bacterial infections in critically ill patients must be quickly and effectively treated to avoid death. Thus, target plasma concentration of amikacin should be achieved on the first attempt. In our hematology-oncology department, we aimed to determine if children with chemo-induced febrile neutropenia (FN) and who are exposed to amikacin achieve target plasma concentration with the currently recommended amikacin dose (15-30 mg/kg).

Methods. Amikacin pharmacokinetic data from 60 children with chemo-induced FN, corresponding to 126 events were analyzed. Using a mono-compartmental linear model, we calculated theoretical amikacin maximal concentration (Cmax) for each event to determine percentage of target attainment (%TA) in dosing clusters.

Results. Fifty-six percent of patients who received an amikacin dose < 20 mg/kg achieved plasma concentration target (Cmax > 60 mg/L), versus 75 % of patients with an amikacin dose ≥ 20 mg/kg. Cmax was higher in patients receiving ≥ 20 mg/kg than those receiving < 20 mg/kg (77.1 ± 24.4 vs 67.8 ± 24.0 mg/L; p =0.033). Patients with amikacin < 20 mg/kg who reached target had a significantly lower volume of distribution (Vd/kg) than patients who did not. Patients with a body weight < 12 kg had lower %TA (p = 0.007) and Cmax (p = 0.011) and a higher Vd/kg (p <0.001) than other patients.

Conclusion. We suggest an upfront amikacin dose of 20-30 mg/kg in children with chemo-induced FN to achieve the target plasma concentration with the first infusion. Monitoring amikacin plasma concentrations remains crucial to insure efficacy and prevent toxicity.