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[Vancomycin: what dosages are needed to achieve efficacy in paediatric hematology/oncology?]

H Zegbeh, N Bleyzac, C Berhoune, Y Bertrand
Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie 2011, 18 (8): 850-5

INTRODUCTION: In children and infants, the determination of optimal dosages is essential from the beginning of treatments with vancomycin because of the high risk of inadequate serum concentrations and bacterial resistance. Bayesian pharmacokinetic methods can be used to adjust dosages according to serum vancomycin concentrations and the patients' physiopathological characteristics. The aim of this retrospective study was to review the effective dosages of vancomycin in paediatric hematology/oncology, using a bayesian pharmacokinetic method.

PATIENTS AND METHODS: One hundred and sixty-one patients in paediatric hematology/oncology units, aged from 1 month to 18 years, who were treated with vancomycin in continuous infusion, were selected between 2000 and 2010. The influence of initial vancomycin dosages on serum steady-state concentrations (S(sc)) before bayesian adaptation was studied on the basis of dosing recommendations in children and infants (i.e., 40 mg/kg/day). In addition, the S(sc) before bayesian adaptation and the effective dosages determined after bayesian adaptation (E(db)) were analysed according to the patients' age, for an identical dosage of 40 mg/kg/day (± 10%).

RESULTS: The percentage of patients with low S(sc) (i.e.,<10mg/L) was 28.6%, 16%, and 0 when treatment was initiated at less than 40 mg/kg/day (± 10%), at 40 mg/kg/day (± 10%), and at more than 40 mg/kg/day (± 10%), respectively. For an identical initial dosage of 40 mg/kg/day (± 10%), the S(sc) gradually increased as the patients' age increased. The S(sc) were optimal (i.e., between 15 and 20mg/L) in adolescents and children from 6 to 12 years of age, but less than 15 mg/L in children from 2 to 6 years of age and infants. The E(db) gradually increased as the patients' age decreased.

DISCUSSION AND CONCLUSIONS: The choice of initial dosages of vancomycin treatment must take greater account of the patient's age in order to reduce the frequency of inadequate S(sc) before titration. In the absence of nephrotoxic cofactors, we suggest an increase in initial vancomycin dosages in continuous infusion between 40 and 45 mg/kg/day in children from 6 to 12 years old, between 45 and 50mg/kg/day in children from 2 to 6 years old, and between 50 and 55 mg/kg/day in infants, in hematology/oncology. For teenage patients, the standard dosage (i.e., 40 mg/kg/d) seems appropriate.


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