A Retrospective Study Evaluating Neonatal Vancomycin Loading Doses to Achieve a Therapeutic Target

Abstract

Background: Vancomycin is a glycopeptide antibiotic that has been used to treat hospital-acquired gram-positive infections for more than 5 decades. However, the literature is divided regarding the therapeutic advantages of vancomycin loading doses in neonates. Objectives: This study aimed to investigate the effect of vancomycin loading doses on therapeutic target attainment in neonates with sepsis. Methods: A retrospective cohort study was conducted to compare the vancomycin target attainment (area under the curve 0–24 hours/minimum inhibitory concentration ≥400) in neonates before and after the 2019 change in vancomycin prescription guidelines at a neonatal unit in Cape Town, South Africa. As the standard of care, Bayesian modelling software was used to compute the area under the curve from the trough concentrations. Results: Two hundred ten neonates were included. Multivariate regression analysis showed a 2-fold increase in the odds of target attainment among neonates receiving a loading dose of vancomycin. Early target attainment (within 8–12 hours of treatment initiation) was significantly higher in the loading dose group compared with the no loading dose group [97/105 (92.4%) versus 64/105 (61.0%); P < 0.001]. However, the overall proportion of neonates achieving target attainment at 24 hours was similar between groups [73/105 (69.5%) in the loading dose group versus 62/105 (59.0%) in the no loading dose group; P = 0.110]. The nephrotoxicity rates were low [2/105 (1.9%) in the loading dose group and 2/105 (1.9%) in the no loading dose group]. Conclusions: The addition of a vancomycin loading dose to neonates may facilitate early therapeutic target attainment.