Abstract
The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population. The study population consisted of 80 neonates in the neonatal intensive care unit (ICU) from which 165 trough and peak concentrations of vancomycin were obtained. Nonlinear mixed effect modeling was used to develop a population pharmacokinetic model for vancomycin. The stability and predictive ability of the final model were evaluated based on diagnostic plots, normalized prediction distribution errors and the bootstrap method. Serum creatinine (Scr) and body weight were significant covariates on the clearance of vancomycin. The average clearance was 0.309 L/h for a neonate with Scr of 23.3 μmol/L and body weight of 2.9 kg. No obvious ethnic differences in the clearance of vancomycin were found relative to the earlier studies of Caucasian neonates. Moreover, the established model indicated that in patients with a greater renal clearance status, especially Scr < 15 μmol/L, current guideline recommendations would likely not achieve therapeutic area under the concentration-time curve over 24 h/minimum inhibitory concentration (AUC24h/MIC) ≥ 400. The exceptions to this are British National Formulary (2016–2017), Blue Book (2016) and Neofax (2017). Recommended dose regimens for neonates with different Scr levels and postmenstrual ages were estimated based on Monte Carlo simulations and the established model. These findings will be valuable for developing individualized dosage regimens in the neonatal ICU setting.
Highlights
After more than 60 years of widespread clinical use, vancomycin remains the gold standard antibiotic prescribed for the treatment of sepsis caused by coagulase-negative Staphylococci and methicillin-resistant Staphylococcus aureus in neonatal intensive care units (ICU) (Tong et al, 2016)
The following information was retrospectively collected from electronic medical records: gestational age (GA), postmenstrual age (PMA), postnatal age (PNA), body weight (WT), dosing history and concentration of vancomycin, serum creatinine (Scr) levels, clinical laboratory tests of other renal and hepatic functions, and co-administered medications
This study offers initial vancomycin dosing regimen with varying degrees of PMA, WT, and serum creatinine for neonates
Summary
After more than 60 years of widespread clinical use, vancomycin remains the gold standard antibiotic prescribed for the treatment of sepsis caused by coagulase-negative Staphylococci and methicillin-resistant Staphylococcus aureus in neonatal intensive care units (ICU) (Tong et al, 2016). To obtain accurate estimation with this method for individualized therapy, it is crucial that reliable population pharmacokinetic characteristics are known for the target patients. Several population pharmacokinetic studies have been conducted in Caucasian (Seay et al, 1994; Grimsley and Thomson, 1999; Capparelli et al, 2001; Mulla and Pooboni, 2005; Allegaert et al, 2007; Anderson et al, 2007; Marques Minana et al, 2010; Oudin et al, 2011; Mehrotra et al, 2012; Zhao et al, 2013; Frymoyer et al, 2014), Japanese (Kimura, 2002), and Malaysian (Lo et al, 2010) neonates, but a large variability in clearance was observed among groups. The average clearance across all three populations ranged from 0.08 to 0.50 L/h for a neonatal patient with a weight of 3 kg and postmenstrual age (PMA) of 40 weeks
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