High-dose gentamicin in newborn infants: is it safe?

Area of Science:

• Neonatal pharmacology
• Pediatric infectious diseases
• Clinical pharmacy

Background:

• Neonatal gentamicin dosing typically uses lower doses (3-5 mg/kg) than older children (≥7 mg/kg) despite neonates' higher volume of distribution.
• Standard dosing may lead to subtherapeutic levels or increased toxicity risk in neonates.
• Extended-interval dosing strategies are explored to optimize gentamicin therapy in this population.

Purpose of the Study:

• To evaluate an extended-interval, high-dose (6 mg/kg) gentamicin regimen in neonates.
• To assess the safety and efficacy of this regimen by measuring trough plasma concentrations (TPCs) and ototoxicity.
• To identify the frequency of prescription errors associated with this dosing strategy.

Main Methods:

• A retrospective study of gentamicin treatment episodes in a tertiary neonatal unit (2004-2012).
• Dosing intervals were adjusted based on gestational age (GA) and corrected age.
• Trough plasma concentrations (TPCs) were measured before the third dose; ototoxicity was assessed via neonatal hearing screening.

Main Results:

• 509 treatment episodes (440 infants) were analyzed.
• Mean gentamicin TPCs were 1.1 (0.5) mg/L in the first week and 0.8 (0.6) mg/L after the first week.
• Elevated TPCs (≥2.0 mg/L) occurred in 6% of episodes, mainly in term infants with renal impairment.
• Prescription errors (mostly prolonged intervals) occurred in 6.7% of episodes.
• 38 patients failed hearing screening, but only 4 had permanent hearing loss, all with TPCs <2.0 mg/L.

Conclusions:

• The extended-interval, high-dose gentamicin regimen demonstrated a low incidence of elevated TPCs.
• The study found a low rate of prescription errors with this regimen.
• No evidence of gentamicin-associated ototoxicity was observed in this cohort.