Comparison of Amikacin Pharmacokinetics in Neonates Following Implementation of a New Dosage Protocol

• Published in: The journal of pediatric pharmacology and therapeutics Vol. 22; no. 1; pp. 33 - 40
• Main Authors: Hughes, Kaitlin M, Johnson, Peter N, Anderson, Michael P, Sekar, Kris C, Welliver, Robert C, Miller, Jamie L
• Format: Journal Article
• Language: English
• Published: United States Pediatric Pharmacy Advocacy Group 01-01-2017
• Subjects: Clinical Investigations; antibiotic; dosage; amikacin; safety; pharmacokinetics; aminoglycosides; neonate; therapeutic drug monitoring
• ISSN: 1551-6776; 2331-348X
• DOI: 10.5863/1551-6776-22.1.33

The primary aim was to compare attainment of goal serum amikacin concentrations using two dosage regimens in patients admitted to a neonatal intensive care unit. Secondary objectives included comparison of percentages of supratherapeutic trough concentrations, and subtherapeutic and supratherapeutic peak concentrations.
This was an Institutional Review Board-approved, retrospective study of neonates receiving amikacin during January-December 2013 (group 1) and January-December 2014 (group 2). Group 1 received amikacin dosage consistent with published recommendations, whereas group 2 was dosed using a modified protocol that was based on postmenstrual and postnatal age. Goal serum amikacin peak concentration was defined as 20 to 35 mg/L; hence, subtherapeutic and supratherapeutic peak concentrations were defined as <20 mg/L and >35 mg/L, respectively. Supratherapeutic trough concentrations were >8 mg/L. Between-group analysis was performed using Wilcoxon-Mann-Whitney test, Student
-test or χ
, or Fisher exact analysis as appropriate with a p value <0.05.
A total of 278 neonates were included (group 1: n = 144; group 2: n = 134). Most patients were male (60%) and were admitted for prematurity or respiratory distress (77%). The median gestational age in group 1 was 34.4 weeks (range, 30.0-37.9 weeks) versus group 2 at 36.9 weeks (range, 31.4-38.9 weeks), whereas the postnatal age was similar between both groups at 4 days. There was a significant increase in attaining goal peak amikacin concentrations between groups 1 and 2, 34% versus 84%, p < 0.001, and decrease in supratherapeutic peak concentrations, 65% versus 12%, p < 0.001. There was no significant difference in subtherapeutic peak or supratherapeutic trough concentrations.
A modified neonatal amikacin dosage protocol resulted in increased peak amikacin serum concentration compared with published dosage recommendations. Future research should focus on determination of the optimal dosage regimen in neonates.