Pharmacokinetic comparison of nomogram-based and individualized vancomycin regimens in neonates

Abstract

This study compared steady-state concentrations achieved with a dosing strategy using first-dose kinetics to individualize vancomycin regimens with the steady-state concentrations achieved using standardized nomograms. Neonatal intensive care unit patients receiving vancomycin according to published nomograms (phase 1) were compared with patients receiving vancomycin using first-dose pharmacokinetic information to individualize the dosing regimen (phase 2). Retrospective chart review was used to gather demographic and patient-specific pharmacokinetic data. Data collected included gestational and postnatal ages, birth and dosing weights, first-dose peak and trough concentrations, serum creatinine, and information related to infection. Data were analyzed to determine the percentage of therapeutic concentrations at a steady state in each group. Phase 1 included 108 patients given doses according to published nomograms, and phase 2 included 85 patients who received vancomycin with first-dose pharmacokinetics. Steady-state concentrations were collected in 108 patients in phase 1 and 39 patients in phase 2. Both peak and trough concentrations were therapeutic at steady state in 39% in phase 1 versus 63% in phase 2 (p < 0.02). Therapeutic steady-state peak concentrations were achieved in 70% versus 76% while therapeutic steady-state trough concentrations were achieved in 50% versus 82% (p < 0.02) in phase 1 and phase 2, respectively. Compared with the use of nomograms, individualization of vancomycin regimens after the first dose in neonatal patients significantly increased the percentage of patients with target steady-state trough concentrations and with both target peak and trough concentrations. The benefits of individualized dosing were attained without additional venous sampling.