Therapeutic Drug Monitoring of Amikacin in Hospitalized Patients: Outcomes from a Teaching Hospital of Hanoi University of Pharmacy

Abstract

Abstract: Background: Amikacin is an aminoglycoside antibiotic widely used in the management of multidrug-resistant Gram-negative infections. However, its clinical use poses significant challenges due to a narrow therapeutic window, interpatient pharmacokinetic variability, and potential nephrotoxicity and ototoxicity. Therefore, implementation of Therapeutic Drug Monitoring (TDM) of amikacin is considered essential to optimize dosing regimens and ensure both efficacy and safety. Method: A prospective, descriptive study on hospitalized adult patients receiving TDM for amikacin. Patients undergoing dialysis and those lacking accurate or clearly documented sampling time data were excluded from the analysis. Blood samples were collected to estimate peak (Cpeak) and trough (Ctrough) concentrations using a Bayesian pharmacokinetic approach (Precise PK^Rx). The PK/PD targets for therapeutic efficacy and safety were defined as Cpeak/MIC ≥ 8 µg/mL and Ctrough ≤ 2 µg/mL. Results: From August 2024 to May 2025, a total of 45 patients were enrolled in the study, with a median age of 69 years, of whom 64.4% were treated in the intensive care unit (ICU). Amikacin was most frequently prescribed for pneumonia (53.3%) and sepsis/septic shock (35.6%). The predominant pathogens isolated were Klebsiella pneumoniae (38.0%) and Escherichia coli (16.0%). The median initial dose of amikacin was 20 mg/kg [IQR: 7.6 - 32.5]. The mean number of TDM occasions per patient was 1.9 ± 1.1. After the first TDM, 46.7% of patients achieved the target Cpeak, and 82.2% achieved the target Ctrough. The attainment rate for the efficacy target improved from 46.7% after the first TDM to 100% after the fourth and fifth TDM assessments. The target attainment rate for safety remained consistently above 80%. Conclusion: Optimization of amikacin dosing through TDM should be routinely implemented and considered in other hospitals to ensure both efficacy and safety in the treatment of severe multidrug-resistant infections.

Keywords: Amikacin, Therapeutic Drug Monitoring (TDM), Multidrug-Resistant Bacteria, Dose Optimization, High-Dose Amikacin.