title: Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates.
abstract: 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.
authors.affiliation: Department of Paediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France EA7323, Université Paris Diderot-Université Paris Descartes, Paris, France Department of Neonatology, CHU de Rennes, Rennes, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Leroux
authors.affiliation: Department of Paediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France EA7323, Université Paris Diderot-Université Paris Descartes, Paris, France Clinical Investigation Center CIC1426, INSERM, Paris, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
authors.affiliation: Neonatal Intensive Care Unit, Hôpital Robert Debré, APHP, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Biran
authors.affiliation: Neonatal and Pediatric Intensive Care Unit, Hôpital Clocheville, Tours, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lopez
authors.affiliation: Neonatal Intensive Care Unit, Hôpital Cochin Port-Royal, APHP, Paris, France.
authors.forename: Doriane
authors.initials: D
authors.lastname: Madeleneau
authors.affiliation: Neonatal and Pediatric Intensive Care Unit, Hôpital Clocheville, Tours, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Wallon
authors.affiliation: Neonatal Intensive Care Unit, Hôpital Cochin Port-Royal, APHP, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Zana-Taïeb
authors.affiliation: Neonatal Intensive Care Unit, Hôpital Robert Debré, APHP, Paris, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Virlouvet
authors.affiliation: Neonatal Intensive Care Unit, Hôpital Robert Debré, APHP, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rioualen
authors.affiliation: Department of Pharmacy, Qian-Fo-Shan Hospital, Shandong University, Jian, China Sino-French Pediatric Research Center, Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China wei.zhao@rdb.aphp.fr.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000706:statistics & numerical data*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D015233:Models, Statistical; D061214:Patient Safety; D057285:Precision Medicine; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin