Is There a Utility of Gentamicin Trough Level Monitoring in Neonates with Presumed Early Onset Neonatal Sepsis?

Background: Gentamicin is one of the most commonly used empiric antibiotics in neonates. The effect of gentamicin is concentration dependent. It requires monitoring in neonates to avoid adverse effects or complications associated with high gentamicin serum concentration including hearing loss and renal impairment. These complications are more closely related to the total amount of drug in the circulation, thereby the measurement before the next dose of gentamicin (gentamicin trough) becomes paramount. Elevated trough levels require increase in drug dose interval to prevent further accumulation of the drug and associated complications. The additional cost, extra blood draw and clinical utility of gentamicin level monitoring has not been well examined in neonates for short-term gentamicin therapy. The objective of this study was to assess the utility of gentamicin trough levels in neonates with presumed early onset neonatal sepsis (EONS) for a short-term gentamicin therapy.

Methods: This is a retrospective cross-sectional study, performed at a Level III NICU. The data was collected from January 2017 to August 2020 from a NICU database. Neonates with presumed EONS with negative blood culture were included in the study. These infants received short-term antibiotic empiric therapy for 2-3 days. Gentamicin was administered by intravenous infusion, with an individualized dose and interval depending on the gestational age. Serum gentamicin trough level was obtained 1 hour before administration of the second dose. If the gentamicin trough level was > 1 mg/L, the dosing interval was increased by 12 hrs. Renal function was evaluated by urine output. A routine hearing screening was performed on all infants after completion of therapy.

Results: A total of 357 infants with gestational age 27-41 weeks received gentamicin for presumed EONS during the study period. The first gentamicin trough level ranges from 0.6-3.5 mg/L with 38.4% neonates had trough level of ≤ 1 mg/L, 54.4 % were 1.1-2 mg/L and only 7.3% were more than 2 mg/L (figure 1). A total of 168 infants (47%) required multiple trough levels (table 1). Overall, 539 tests performed during the study period, which cost $67,375 considering a charge of $125/test. None of these infants had clinical signs of renal dysfunction. Of 357 infants, 346 (96.9%) passed hearing screen test before discharge and 12 (3.4%) had referred hearing screen. All 12 infants passed hearing screen on subsequent audiology evaluation. None of the infants with gentamicin trough level of >2 mg/L had renal dysfunction or hearing loss.

Conclusion: Gentamicin trough monitoring does not yield a significant value in neonates with presumed sepsis who require short-term antibiotic therapy. Further larger studies are needed to evaluate the relatively rare outcome of hearing loss and nephrotoxicity with short-term empiric gentamicin therapy. A more targeted approach to screen gentamicin level monitoring could be a cost-effective strategy in neonates.