PC1131: Pharmacokinetics of Gentamicin in Late Preterm, Early Term, and Term Neonates: A Retrospective Study

Background: Aminoglycosides are broad-spectrum antibiotics used widely in the management of early-onset sepsis in neonates. The current standard recommendation in NeoFax®-Micromedex prescribes the same dose of gentamicin (4 mg/kg) for all neonates ≥ 35 weeks of completed gestation. But we hypothesize differences in the pharmacokinetics of gentamicin (gentamicin trough GT, peak GP, first order rate constant Ke, volume of distribution Vd, half-life t1/2, and clearance CLag) between late preterm (LPT, 35 <= GA < 37 weeks), early term (ET, 37 <= GA < 39 weeks), and term (T, GA ≥ 39 weeks) neonates. Our aim is to ascertain if there exists any significant difference in the gentamicin pharmacokinetics between LPTs, ETs, and Ts.
Secondly, we also aim to assess the association, if any, between a compound perinatal asphyxia risk (PAR) score, based on maternal and fetal factors which increase the risk for perinatal asphyxiation, and the pharmacokinetics of gentamicin in LPTs, ETs, and Ts.

Methods: Retrospective cross-sectional study on all neonates (LPT, ET, and T) who were managed for suspected or proven sepsis at the Brookdale NICU between July 1, 2016 to June 30, 2021.
The pharmacokinetic parameters were calculated using the standard first-order pharmacokinetic model.
The relationship between the respective cohorts of GAs and PARs was assessed with one-way ANOVA and independent t-test, respectively. A p-value < 0.05 was considered significant.

Results: Neonates with prenatally diagnosed renal pathologies, missing gentamicin trough/peak, serum creatinine, or cord blood gases were excluded and a total of 460 cases (12% LPT, 33% ET, and 55% T) were available for the study (Table 1).
Significant differences in GT, Vd, and CLag were noted between the LPTs and Ts. The mean trough level in LPTs was 13% higher than the Ts while the Vd and CLag were 30% and 20% lower, respectively, in the LPTs (Table 2).
The analysis on the PAR cohorts revealed a higher mean trough level (27% higher) in the higher PAR score group than the lower PAR score group for the LPTs.

Conclusion: LPTs have different pharmacokinetics of gentamicin compared to the Ts, with a lower mean Vd and CLag and consequently a higher mean trough level than the Ts.
Within the LPT group, the presence of a higher PAR score is associated with a higher mean gentamicin trough level.
Therefore, it might be prudent to adjust the dosage of Gentamicin in LPTs to reduce the risk of adverse effects. A further dose adjustment may be necessary within the LPTs based on assessment of risk for perinatal asphyxiation.
The limitations of this study are its retrospective design and variability in documentation of dosage and sampling times.