Continuous infusion of vancomycin in neonates

Patel, Anisa D; Anand, Dhullipala; Lucas, Carol; Thomson, Alison

doi:10.1136/archdischild-2012-303197

Cited by 28 publications

(38 citation statements)

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“…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). In accordance with reported clinical practice in adults, continu-ous dosing has also been investigated in neonates, infants, and children (31,34,(46)(47)(48)(49).…”

mentioning

confidence: 81%

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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mentioning

confidence: 81%

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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“…Hay aparición progresiva de literatura científica que plantea como concentración terapéutica objetivo en neonatos valores de 20-25 μg/L, especialmente en los pacientes críticos. Sin embargo, en la población neonatal este rango se alcanza sólo en 46% de los pacientes y hasta en un 20-25% las concentraciones son menores a 10 μg/mL 12,13 . La imposibilidad de alcanzar concentraciones óptimas lleva a reajustar constantemente las dosis alcanzando incluso dosis de hasta 80 mg/kg/día.…”

Section: Concentraciones Plasmáticasunclassified

“…La imposibilidad de alcanzar concentraciones óptimas lleva a reajustar constantemente las dosis alcanzando incluso dosis de hasta 80 mg/kg/día. Este problema se debe entre otras cosas a la diferencia inter-individual de esta población en cuanto a sus volúmenes de distribución y al creciente aumento de la CIM de vancomicina 13 , que puede llegar a ser 2 µg/ml para SCN. 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.…”

Section: Concentraciones Plasmáticasunclassified

“…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

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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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“…A continuous infusion might be beneficial in providing greater time at a concentration above the MIC of the organism being treated and could make both administration and monitoring easier, provided there is adequate venous access. These issues are also of interest in the neonatal population, and there have been some recent publications suggesting the use of a loading dose and then continuous infusion for neonates to achieve better vancomycin levels 23 24. This needs further investigation in children to establish the correct loading dose and total daily dose required in the infusion to achieve optimal vancomycin levels.…”

Section: What About a Loading Dose And/or Continuous Infusions Of Vanmentioning

confidence: 99%

Vancomycin dosing in children: what is the question?

Cole

Riordan

2013

Arch Dis Child

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Vancomycin has been in clinical use for over 60 years, but it is still not clear what dose should be given to children. Effective treatment with vancomycin requires a serum concentration well above the minimum inhibitory concentration (MIC) of the bacteria being treated. This is predicted by the area under the concentration curve (AUC) divided by the MIC being >400 (AUC/MIC). Recent concerns about increasing MIC in staphylococci have lead to recommendations to aim for higher trough vancomycin levels (15-20 mg/L). In current practice, most children do not achieve these trough levels. Modelling and pharmacokinetic studies in children suggest these trough levels may not be necessary if the MIC of the organisms is 1 mg/L or less. Further, large-scale studies are needed to determine the most appropriate dosing of vancomycin in children. While awaiting these, it is time to consider moving to 15 mg/kg 6 h as a standard starting regime for vancomycin. It is also vital to determine the MIC of the organism being treated, as this may give some guidance about suitable trough levels to be aimed for. There is currently little evidence to guide the use of loading doses or continuous vancomycin infusions in children.

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Continuous infusion of vancomycin in neonates

Cited by 28 publications

References 4 publications

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

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

Vancomycin dosing in children: what is the question?

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