Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

Stéphanie Leroux (1, 2, 3) , Evelyne Jacqz-Aigrain (4, 1, 3) , Valérie Biran (5) , Emmanuel Lopez (6) , Doriane Madeleneau (7) , Camille Wallon (6) , Elodie Zana-Taïeb (7) , Anne-Laure Virlouvet (5) , Stéphane Rioualen (5) , Wei Zhao (8)

1 EA_7323 - Evaluation thérapeutique et pharmacologie périnatale et pédiatrique
2 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
3 Service de Pharmacologie Pédiatrique et Pharmacogénétique [Robert Debré, Paris]
4 CIC 1426 - Centre d'Investigation Clinique 1426
5 Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré]
6 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
7 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
8 Shandong Jiaotong University [Jinan]

Pharmacokinetic modeling has often been applied to evaluate vancomycin pharmacokinetics in neonates. However, clinical application of the model-based personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a model-based patient-tailored dose of vancomycin in neonates. A model-based vancomycin dosing calculator, developed from a population pharmacokinetic study, has been integrated into the routine clinical care in 3 neonatal intensive care units (Robert Debré, Cochin Port Royal, and Clocheville hospitals) between 2012 and 2014. The target attainment rate, defined as the percentage of patients with a first therapeutic drug monitoring serum vancomycin concentration achieving the target window of 15 to 25 mg/liter, was selected as an endpoint for evaluating the clinical utility. The safety evaluation was focused on nephrotoxicity. The clinical application of the model-based patient-tailored dose of vancomycin has been demonstrated in 190 neonates. The mean (standard deviation) gestational and postnatal ages of the study population were 31.1 (4.9) weeks and 16.7 (21.7) days, respectively. The target attainment rate increased from 41% to 72% without any case of vancomycin-related nephrotoxicity. This proof-of-concept study provides evidence for integrating model-based antimicrobial therapy in neonatal routine care.

Domaines: Pharmacologie; Pédiatrie

Stéphanie Leroux, Evelyne Jacqz-Aigrain, Valérie Biran, Emmanuel Lopez, Doriane Madeleneau, et al.. Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates. Antimicrobial Agents and Chemotherapy, 2016, 60 (4), pp.2039-2042. ⟨10.1128/AAC.02214-15⟩. ⟨hal-01435013⟩