STUDY OBJECTIVE: To compare four common dosing regimens for vancomycin in 
preterm and term neonates by assessing the probability that each regimen would 
achieve the widely used therapeutic target serum trough concentrations of 5-15 
mg/L and the newly suggested target of 15-20 mg/L.
DESIGN: Retrospective population pharmacokinetic analysis using therapeutic drug 
monitoring data obtained from 1990-2007, with a subsequent simulation study 
performed on the pharmacokinetic model.
SETTING: Tertiary-care children's hospital.
PATIENTS: One hundred thirty-four preterm (66%) and term (34%) neonates, with a 
postnatal age of 1-121 days and postmenstrual age of 24.6-44 weeks.
MEASUREMENTS AND MAIN RESULTS: Therapeutic drug monitoring data for vancomycin 
were used to develop a population pharmacokinetic model in the target 
population. Parameter estimates for the derived pharmacostatistical model were 
used to perform Monte Carlo simulations for four recommended dosing regimens: a 
standard dose for all neonates, postmenstrual age-based dosing, postmenstrual 
and postnatal age-based dosing, and serum creatinine-based dosing. Multivariate 
age-weight distributions were established for term and preterm neonates using 
Centers for Disease Control and Prevention growth charts and intrauterine and 
postnatal growth charts from the literature, respectively. Each dosing regimen 
was treated as a separate scenario in which 200 replicates with 100 
patients/replicate were simulated. The 5-15-mg/L target trough serum 
concentration was achieved in 34% (90% confidence interval [CI] 20-53%), 42% 
(90% CI 31-55%), 52% (90% CI 43-60%), and 63% (90% CI 54-72%) of patients 
receiving the standard dose, postmenstrual age-based dose, postmenstrual and 
postnatal age-based dose, and serum creatinine-based dose, respectively. Serum 
creatinine-based dosing produced trough concentrations predominantly in the 
5-15-mg/L target range, with the smallest variability in both term and preterm 
neonates. As expected, when the target range was narrow and higher (15-20 mg/L), 
only 13-21% of patients were within the range across the four dosing regimens.
CONCLUSION: Monte Carlo simulations based on our population pharmacokinetic 
model suggest that vancomycin dosing guidelines based on serum creatinine 
concentration have a greater likelihood of achieving trough concentrations in 
the 5-15-mg/L range compared with other evaluated dosing regimens. None of the 
four dosing regimens is suitable to produce target trough concentration of 15-20 
mg/L in an acceptable number of patients.