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

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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.


Presented at the 114th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics