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

Abstract

OBJECTIVESThe 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. METHODSThis 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 t-test or χ 2 , or Fisher exact analysis as appropriate with a p value <0.05. RESULTSA 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.CONCLUSIONS 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.

Amikacin: Uses, Resistance, and Prospects for Inhibition

“…Amikacin is used to treat infections in neonates, including preterm neonates [ 42 , 125 , 145 , 146 , 147 ]. Although it has been successful in treating infections caused by multidrug resistant strains [ 126 , 148 , 149 ] there are still controversies about dosage and pharmacokinetics [ 126 , 146 ]. Unfortunately, the recent rise in resistance to amikacin limits the effectivity of many interventions during outbreaks of infection in neonates [ 41 , 42 , 150 ].…”

Causative organisms and antimicrobial susceptibility in jaundiced infants with significant bacteriuria

“…Many previous reports have shown that potential adverse effects, including nephrotoxicity in amikacin, were no more than gentamicin in neonates. 38–40 We suggest that modification of current empiric antibiotics for amikacin-based regimens should be considered, mainly in newborn infants with Gram-negative bacterial infections.…”

Assessment of flomoxef combined with amikacin in a hollow-fibre infection model for the treatment of neonatal sepsis in low- and middle-income healthcare settings

“…PK profiles of flomoxef and amikacin were designed to have half-lives of 2.3 and 7 h, with C max values of 50 and 40 mg/L, respectively, to reflect the median neonatal time–concentration profile following an administration of 20 mg/kg IV dose of flomoxef 31 and 15 mg/kg amikacin. 40 These were determined from the sources used to determine the half-life, as described earlier. Each individual experiment consisted of four arms; monotherapy arms for both flomoxef and amikacin, a combination therapy arm and an untreated control.…”