Neonatal Population Pharmacokinetics and Pharmacodynamics Modeling of Vancomycin to Simulate Target Exposure Attainment

ACKGROUND

Vancomycin is bactericidal against gram-positive organisms, including coagulase (+) and coagulase (-) Staphylococci. Several professional societies have recommended a ratio of area under the curve to minimum inhibitory concentration (AUC:MIC) >400, which has been associated with optimal adult outcomes. The objectives of this neonatal study were: 1) to construct a population PK/PD model for vancomycin serum concentrations and 2) to simulate the proportion who achieved an AUC:MIC >400. METHODS Population PK/PD modeling using NONMEM was conducted. Neonatal data (1 vancomycin serum concentration(s) from 2006-2011 were obtained from electronic medical records. These data were not complete before October 1, 2012. RESULTS A one compartment, first order elimination model evaluated 1081 vancomycin concentrations from 222 neonates. Estimated CL was 0.107 L/hr/kg and Vd was 1.10 L/kg. Coagulase (+) Staphylococci MIC values ranged from 0.5-2 mg/L and coagulase (-) Staphylococci MIC values ranged from 0.5-4 mg/L. Doses of 40 and 60 mg/kg/day infrequently achieved the AUC:MIC target of >400. CONCLUSION Conventional neonatal vancomycin dosing regimens infrequently achieve an adult PK/PD target associated with optimal bactericidal activity. Further research is needed to evaluate the clinical efficacy of this target in neonates.