A Retrospective Study of Amikacin Dosage Adequacy Based on Therapeutic Drug Monitoring in Neonates in a Tertiary Care Hospital in Kelantan, Malaysia

Abstract

Body weight, age, and kidney function especially in neonates, significantly influence amikacin distribution and/or clearance, causing large pharmacokinetics variability, which directly effects minimum and maximum concentrations (Cmin and Cmax, respectively) when coupled with amikacin dose regimen. This study aims to investigate amikacin dose adequacy based on therapeutic drug monitoring (TDM) results obtained from neonatal patients. A retrospective study was conducted from July to September 2020 at Hospital Raja Perempuan Zainab II, Kelantan, Malaysia. A total of 229 blood samples were collected from neonates who were prescribed amikacin and had TDM performed from 1st January to 31st December 2019. The data is analysed using Statistical Package for Social Sciences (SPSS) version 25.0. The significance level is set at p<0.05. Out of the total, 113 (49.3%) neonates were prescribed amikacin doses of <7.5 mg/kg/day, while another 110 neonates (48.0%) received doses between 7.5 to 15 mg/kg/day. The remaining 2.7% (n = 6) of neonates received doses above 15 mg/kg/day. The results showed that 95.2% (n = 218) neonates achieved therapeutic Cmin of <5 mg/L. Most neonates (80.8%) had inadequate Cmax with only 19.2% (n = 44) accomplishing therapeutic Cmax of ≥20 mg/L. Preterm neonates were shown to achieve the most therapeutic Cmax (61.4%) followed by term neonates (38.6%). Neonates who achieved the target Cmax were prescribed a dosing regimen of 7.5 to 15 mg/kg/day (12.2%) with a mean + SD amikacin dose of 9.39 ± 3.01 mg/kg/day in this study. Almost 50% of amikacin doses prescribed for the study population were below the recommendations in the common dose guidelines, contributing to amikacin dosage inadequacy. Future detailed studies are needed to further investigate other factors associated with amikacin dose adequacy in neonates and to develop neonatal population pharmacokinetics model of amikacin