Amikacin use in critically ill patients requiring renal replacement therapy: the AMIDIAL-ICU study.

BACKGROUND

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is common in intensive care units (ICUs), yet optimal amikacin dosing in this context remains poorly understood.

METHODS

We conducted a prospective observational study across 18 French hospitals from April 2020 to January 2022. Adult ICU patients (aged > 18 years) receiving their first amikacin dose while on RRT were included. Data on demographics, RRT modalities, amikacin dosing, and therapeutic drug monitoring were collected. Using a pharmacokinetic modeling approach, we evaluated various amikacin regimens and simulated target attainment probabilities across different minimum inhibitory concentrations (MICs).

RESULTS

A total of 111 patients were included, with approximately two-thirds receiving continuous RRT. The median amikacin dose was 27 (25-30) mg/kg. Amikacin peak (Cmax) and trough concentrations were monitored in 53 (47.8%) and 76 (68.5%) patients, respectively. Continuous RRT and a history of chronic kidney disease reduced dialytic clearance. For a MIC ≤ 4 mg/L, a 15 mg/kg amikacin dose achieved Cmax/MIC and AUC/MIC targets in ≥ 90% of patients on intermittent dialysis, while 20 mg/kg was required for those on continuous dialysis. For a MIC = 8 mg/L, a 30 mg/kg dose was necessary to achieve Cmax/MIC ≥ 8.

CONCLUSIONS

Our findings highlight suboptimal adherence to amikacin monitoring guidelines in ICU patients on RRT. Using pharmacokinetic modeling, we identified amikacin dosing recommendations ranging from 15 to 35 mg/kg to optimize efficacy and minimize risks, depending on MIC and dialysis modality.