Population pharmacokinetics of amikacin in patients with a haematological disorder: A prospective, observational study.

OBJECTIVES

To assess amikacin target attainment in patients with a haematological disorder treated for febrile neutropenia or severe infection and to develop a population pharmacokinetic (PK) model.

METHODS

This prospective observational single-centre study was conducted at the University Hospital Basel, Switzerland between December 2022 and February 2024. Adult patients with a haematological disorder treated with amikacin for 1-3 days were included. Total amikacin concentrations in blood were measured 1 h and 8 h after each administration. The primary objective was target attainment (Cmax ≥60 mg/L) at all time points evaluated (in the context of the amikacin ECOFF of 8 mg/L for Enterobacterales). A population PK model was developed to derive individual exposure estimates.

RESULTS

Overall, 57 patients with 119 amikacin applications and 174 concentration measurements were included. The median age was 61 years [interquartile range (IQR) 53-68] and 33% were female. Targets of Cmax ≥60 mg/L were attained in 11/57 patients (19.3%) and Cmax/MIC≥8 in 10/10 patients (100%), in whom a pathogen was identified. In the population PK model, weight and GFR were correlated with PK parameters in the multivariable analysis.

CONCLUSIONS

Amikacin target attainment was low in patients with a haematological malignancy treated empirically for FN, when pathogens with higher MICs are considered. Dosing optimisation may be needed to improve target attainment.