Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring

Zhao, Wei; López, E.; Biran, Valérie; Durrmeyer, Xavier; Fakhoury, May; Jacqz-Aigrain, Évelyne

doi:10.1136/archdischild-2012-302765

Cited by 108 publications

(106 citation statements)

References 16 publications

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“…Individual dosage prescription and adjustment based on these covariates will require a computer-based tool. This practice has been set up in our neonatal intensive care unit (NICU) to individualize vancomycin dosing in neonates (25) and undoubtedly will be implemented for the treatment of pediatric patients with selected diseases.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Zhao

Zhang

Fakhoury

et al. 2014

Antimicrob Agents Chemother

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e An increase in vancomycin dose has been proposed in adults with malignant hematological disease. As pediatric data are limited, our aim was to evaluate the population pharmacokinetics of vancomycin in order to define the appropriate dosing regimen in children with malignant hematological disease. Vancomycin concentrations were collected prospectively during therapeutic monitoring. Population pharmacokinetic analysis was performed using NONMEM software. Seventy children (age range, 0.3 to 17.7 years) were included. With the current recommended dosing regimen of 40 to 60 mg/kg/day, 53 children (76%) had subtherapeutic steady-state trough concentrations (C ss/min of <10 mg/liter). A one-compartment model with first-order elimination was developed. Systematic covariate analysis identified that weight significantly influenced clearance (CL) and volume of distribution (V) with power functions of 0.677 for CL and 0.838 for V. Vancomycin CL also significantly increased with increases in creatinine clearance and seemed to be higher in children with malignant hematological disease than in the general pediatric population. The model was validated internally. Its predictive performance was further confirmed in an external validation by Bayesian estimation. A patient-tailored dosing regimen was developed based on the final pharmacokinetic model and showed that a higher proportion of patients reached the target C ss/min than with the traditional mg/kg-basis dose (60% versus 49%) and that the risks associated with underdosing or overdosing were reduced. This is the first population pharmacokinetic study of vancomycin in children with malignant hematological disease. An optimized dosing regimen, taking into account patient weight, creatinine clearance, and susceptibility of the pathogens involved, could routinely be used to individualize vancomycin therapy in this vulnerable population.

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Zhao

Zhang

Fakhoury

et al. 2014

Antimicrob Agents Chemother

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“…The exposure or AUC of vancomycin is dependent on the primary pharmacokinetic parameter total body clearance, which is known to vary widely between infants and children of different ages, especially in the heterogeneous group of preterm neonates (19,20,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). Despite the large number of proposed vancomycin dosing regimens currently available for neonates and infants (10,11,(37)(38)(39)(40)(41), studies reporting on the results of therapeutic drug monitoring show that the target trough concentrations are difficult to attain in clinical practice (42)(43)(44)(45).…”

mentioning

confidence: 99%

Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling

Janssen

Välitalo

Allegaert

et al. 2016

Antimicrob Agents Chemother

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iBecause of the recent awareness that vancomycin doses should aim to meet a target area under the concentration-time curve (AUC) instead of trough concentrations, more aggressive dosing regimens are warranted also in the pediatric population. In this study, both neonatal and pediatric pharmacokinetic models for vancomycin were externally evaluated and subsequently used to derive model-based dosing algorithms for neonates, infants, and children. For the external validation, predictions from previously published pharmacokinetic models were compared to new data. Simulations were performed in order to evaluate current dosing regimens and to propose a model-based dosing algorithm. The AUC/MIC over 24 h (AUC 24 /MIC) was evaluated for all investigated dosing schedules (target of >400), without any concentration exceeding 40 mg/liter. Both the neonatal and pediatric models of vancomycin performed well in the external data sets, resulting in concentrations that were predicted correctly and without bias. For neonates, a dosing algorithm based on body weight at birth and postnatal age is proposed, with daily doses divided over three to four doses. For infants aged <1 year, doses between 32 and 60 mg/kg/day over four doses are proposed, while above 1 year of age, 60 mg/kg/day seems appropriate. As the time to reach steady-state concentrations varies from 155 h in preterm infants to 36 h in children aged >1 year, an initial loading dose is proposed. Based on the externally validated neonatal and pediatric vancomycin models, novel dosing algorithms are proposed for neonates and children aged <1 year. For children aged 1 year and older, the currently advised maintenance dose of 60 mg/kg/day seems appropriate. In the pediatric population, drugs are often administered in an off-label or unlicensed manner (1). While pediatric dosing regimens are mostly empirically derived using extrapolations based on body weight (2, 3), it has been shown before that dosing in children should be guided by the understanding of developmental changes in the pharmacokinetic and/or pharmacodynamic relation of drugs (2, 4, 5). More specifically, translation of results from pharmacokinetic modeling studies has been shown to result in individualized dosing guidelines for many different drugs in pediatric clinical practice (5-9).The antibacterial agent vancomycin is commonly used to treat infections caused by Gram-positive organisms, like methicillinresistant Staphylococcus aureus (MRSA) and amoxicillin-resistant Enterococcus species, in both adults and pediatric patients (10). In neonates, MRSA infection is relatively rare, and coagulase-negative staphylococci are the most commonly identified infectious organisms necessitating vancomycin treatment (11,12). For vancomycin, it has been shown that bacterial killing of S. aureus is best predicted by the area under the concentration-time curve over 24 h (AUC 24 ) divided by the MIC for the infecting pathogen (AUC 24 / MIC) (13-15). In adult patients, an AUC 24 /MIC of Ն400 resulted in a superior clinical and...

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“…Lo anterior ha generado una tendencia a utilizar protocolos de infusión continua o prolongadas de vancomicina basados en el peso, edad gestacional corregida y creatininemia. Las ventajas del uso de la infusión continua o prolongada es que se logran concentraciones plasmáticas más estables y óptimas 13 ; sin embargo, existen pocos estudios en población neonatal y por ahora en la práctica clínica es poco realizable, debido al bajo peso de estos pacientes y a las múltiples infusiones que reciben en forma simultánea 12,14 . En base a lo expuesto sobre las concentraciones plas-Infectología al Día máticas terapéuticas, lamentablemente faltan estudios para definir la forma óptima de realizar el cálculo de la dosificación de vancomicina en neonatos 12 .…”

Section: Concentraciones Plasmáticasunclassified

Reposicionando la cloxacilina como antibioticoterapia empírica inicial de la sepsis tardía neonatal

Sandoval

Cofré

Delpiano

et al. 2015

Rev. chil. infectol.

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Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring

Abstract: A patient-tailored optimised dosing regimen should be used routinely to individualise vancomycin continuous infusion therapy in neonates.

Cited by 108 publications

References 16 publications

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling

Reposicionando la cloxacilina como antibioticoterapia empírica inicial de la sepsis tardía neonatal

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