A pilot study on the use of amikacin in neonates: Who should be monitored for ototoxicity?

Background: Aminoglycosides (AGs) cause irreversible hearing loss. The toxic effects of AGs are dose dependent and correlate with increasing drug serum concentrations. Method: Purposive sampling was used to identify newborn infants in the neonatal intensive care unit who had been initiated on amikacin therapy. Distortion product otoacoustic emission (DPOAE) testing, as the baseline for outer hair cell functioning, was performed. The tests were repeated on the third day of therapy, and therapeutic drug monitoring performed using a one-compartment, open pharmacokinetic model. Results: The neonates who were classified as extremely preterm (n = 5), had a mean peak amikacin level of 50.91 µg/ml (± 10.59 µg/ml), the very preterm neonates (n = 9) a mean peak of 53.29 µg/ml (± 18.49 µg/ml), the moderate- to late-preterm neonates (n = 2) 54.15 µg/ml (± 0.76 µg/ml), and the full-term neonates (n = 6) 43.38 µg/ml (± 10.08 µg/ml). The mean trough level was the highest in the extremely preterm category, at 7.31 µg/ml (± 3.19 µg/ml). The mean trough concentrations were 5.23 µg/ml (± 5.17 µg/ml) in the very preterm neonates, 5.69 µg/ml (± 6.97 µg/ml) in moderate- to late-preterm neonates, and 2.51 µg/ml (± 1.39 µg/ml) in the full-term neonates. There was a change in the DPOAE test amplitude reading between baseline and follow-up of more than 2.4 dB sound pressure level, at one or more frequency levels, in 13 neonates (59%, n = 22). Conclusion: Premature neonates should be the target population when monitoring the pharmacokinetics of ototoxic medication and when performing diagnostic DPOAE testing.