Therapeutic drug monitoring of amikacin in preterm and term infants

Abstract

Introduction: Amikacin is a commonly-prescribed drug used for the empirical treatment of bacterial infections in neonates. A marked change in the pharmacokinetics of amikacin has been reported during neonatal life. Amikacin has a very narrow therapeutic range and can cause very serious side effects such as nephrotoxicity and ototoxicity. The current therapeutic dose of amikacin, i.e. 15 mg/kg of body weight, may increase the risk of toxicity in preterm infants with immature renal functions. We aimed to determine the frequency of amikacin toxicity in preterm as compared to term infants by measuring its serum trough levels following the administration of the current therapeutic dose.

Methods: A comparative study was conducted at the neonatal intensive care unit of the Military Hospital, Rawalpindi, Pakistan. A total of 104 infants (52 term and 52 preterm) receiving amikacin at a dose of 15 mg/kg of their body weight, once daily for bacterial infection, were included. After clinical evaluation, serum creatinine levels were measured at admission and on the third day. Amikacin trough levels were taken after 72 hours of therapy and measured on the TDx Abbot Drug Analyser.

Results: The gestational age range was 37-40 weeks in term and 29-36 weeks in preterm infants. The term and preterm infants had a median weight of 2.8 kg and 2.1 kg, respectively. The preterm infants had significantly higher median (range) 11.33 (1.50-42.60) ug/ml levels of serum amikacin as compared to 8.5 (2.8-33.0) ug/ml in term infants (p-value is less than 0.01). The preterm infants had a high frequency of toxic 32 (62 percent) and subtherapeutic 12 (23 percent) levels, as compared to 11 (21 percent) and 5 (10 percent) in term infants, respectively. Serum amikacin levels revealed a positive correlation with post-dose serum creatinine (r equals 0.48; p-value is less than 0.05).

Conclusion: This study demonstrated that the current practice of amikacin treatment for bacterial infection needs to be adjusted due to unique pharmacokinetic variability in preterm infants. There is a need for regular therapeutic drug monitoring and renal function assessment in all infants receiving amikacin therapy in order to avoid nephrotoxicity.