Gentamicin therapeutic drug monitoring in neonates : an observational study

Abstract

BACKGROUND: Gentamicin is important in the treatment of suspected neonatal sepsis, while also potentially oto- and nephrotoxic. Therapeutic drug monitoring of serum gentamicin levels (SGL) helps to prevent this. We present an investigation into the influence of birthweight, gestational age, and appropriateness-for-gestational age on the rates of high SGLs amongst neonates treated for suspected sepsis.

METHODS: Case notes of neonates admitted to the neonatal and paediatric intensive care unit from 2013-2017 who received intravenous gentamicin treatment were reviewed. The dosing regimen, SGL, and demographic details were recorded. Trough SGLs ≥2mg/L before the 2nd gentamicin dose were taken as indicative of unsafe levels. Mean SGLs and percentage of safe SGLs were compared for each category (birthweight, gestational age, appropriateness-of-weight-for-gestational age) using odds ratios (Student’s t-test), ‘N-1’ Chi squared test, and correlation coefficient.

RESULTS: In total 170 neonatal gentamicin results were analysed. Nineteen (11.2%) of these were ³2mg/L. Stratifying the results according to birthweight showed significantly higher mean gentamicin levels in neonates weighing <1.5kg (1.34mg/L; 95% CI: 1.16-1.53) and 1.5-3kg (1.33mg/L; 95% CI: 1.13-1.52), compared to those weighing >3kg (0.71mg/L; 95% CI 0.57-0.85). Premature neonates born at 28 weeks’ gestation or less had significantly higher mean gentamicin levels (1.69mg/L; 95% CI: 1.33-2.04) than those born at term (0.84mg/L; 95% CI: 0.68-0.99mg/L).

CONCLUSIONS: While the current gentamicin dosing guidelines are safe, extremely premature neonates born under 28 weeks are at higher risk for high gentamicin trough levels and potential toxicity. Extended interval gentamicin dosing may have a role in mitigating for this.