P3D328: Salivary Sampling as a Noninvasive Method of Monitoring Gentamicin Levels in Neonates

Background: Gentamicin is a commonly used antibiotic for neonatal sepsis and requires invasive blood sampling for therapeutic drug monitoring (TDM). Previous studies comparing salivary to serum concentrations of gentamicin for TDM have shown promising results in older infants and adults with once-daily dosing. The study aim is to determine if salivary and serum gentamicin levels correlate in neonates, when treated with extended interval dosing as recommended by NeoFax.

The primary outcome is the correlation between salivary and serum gentamicin levels at each dosing interval.

Methods: This single-center, prospective, observational study enrolled 23 infants at Walter Reed National Military Medical Center and prescribed gentamicin from birth to 42 weeks postmenstrual age. Infants were enrolled into one of three groups based on standard NeoFax dosing intervals: 1) 35-42 weeks gestational age (GA) receiving 24-hour dosing, 2) 30-34 weeks GA receiving 36-hour dosing, and 3) ≤ 29 weeks GA receiving 48-hour dosing. Paired salivary and blood samples were collected during clinically indicated blood draws during treatment with gentamicin. Gentamicin levels were analyzed via competitive enzyme-linked immunoassay and compared using Pearson’s correlation.

Results: 66 paired samples from 28 neonates (mean GA 38+4 and 32+6 weeks in the 24-hour group and 36-hour groups respectively), were collected and analyzed. 16 samples could not be analyzed due to a dry saliva swab or collection errors. There was a strong correlation between salivary and serum gentamicin concentrations with 36-hour interval dosing during a treatment course in the same patient (correlation coefficient (r) = 0.76, p = 0.003) (figure, table), but the correlation did not persist across all patients in the dosing group (r = 0.4, p = 0.33). There was not a significant correlation in the 24-hour interval group (r = 0.27, p = 0.36). Patient enrollment is ongoing in the 36 and 48-hour dosing interval cohorts.

Conclusion: This is the first study evaluating the correlation between salivary and serum gentamicin levels in the neonatal population when using extended interval dosing. Interim study results suggest salivary gentamicin levels might not significantly correlate with serum levels across the entire neonatal population. Prior publications demonstrated a significant correlation in older children with 24-hour dosing of gentamicin, yet we did not identify a similar correlation. We speculate this may be due to 83% of samples being collected at random times (versus trough levels), which may not have allowed sufficient time for the positively charged gentamicin to enter and equilibrate with saliva, as well as the small sample size, with 24% of the collected samples having no reported results. In conclusion, our interim analysis suggests that salivary sampling may not be a promising method of TDM for gentamicin in preterm infants receiving 24 or 36-hour dosing to decrease invasive blood sampling.