Impact of a Hospitalwide Increase in Empiric Pediatric Vancomycin Dosing on Initial Trough Concentrations

Frymoyer, Adam; Guglielmo, B. Joseph; Wilson, Stephen D.; Scarpace, Sarah; Benet, Leslie Z.; Hersh, Adam L.

doi:10.1592/phco.31.9.871

Cited by 46 publications

(41 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At this moment, several pediatric pharmacokinetic models of vancomycin have been published (19-34, 36, 54-59), but only few individualized, model-based dosing algorithms are available (25,27,30,34,57,59). In clinical practice, target concentrations and AUC 24 /MIC values are hard to achieve (42)(43)(44)(45)60). Simulations based on two models (22,23), that are now validated internally and externally, showed, indeed, that adapted doses are needed, especially for neonates and young infants.…”

Section: Discussionmentioning

confidence: 99%

“…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: 99%

See 1 more Smart Citation

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

Janssen

Välitalo

Allegaert

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Pediatric evidence and adult consensus recommendations published in 2009 through 2011 suggested that higher starting doses (eg, 60 mg/kg/day) may be necessary to achieve serum trough concentrations corresponding to the optimal area under the curve (AUC) for plasma concentration relative to the organism minimum inhibitory concentration (MIC). [13][14][15] Subsequently, pediatric reports emerged suggesting increased incidence of AKI. 7,8 Relative to data in adults, there are fewer pediatric studies evaluating vancomycin-associated AKI, though similar trends have been observed with respect to AKI-associated factors.…”

Section: Introductionmentioning

confidence: 99%

Late-Occurring Vancomycin-Associated Acute Kidney Injury in Children Receiving Prolonged Therapy

et al. 2015

View full text Add to dashboard Cite

Abstract:Background: Acute kidney injury (AKI) in patients receiving vancomycin has been associated with trough concentrations ≥15 mg/L and longer therapy duration. The objective of this study was to determine the incidence and factors associated with late AKI in children receiving ≥8 days of vancomycin therapy.Methods: Children aged 30 days to 17 years who were admitted to our institution and received intravenous vancomycin for at least 8 days during January to December of 2007 and 2010 and had a suspected or proven gram-positive infection were included. Late AKI was categorized as AKI occurring after the first 7 days of therapy and within 48 hours following vancomycin discontinuation. The primary outcome was incidence of late AKI as determined by modified pRIFLE criteria. Results: One-hundred sixty-seven patients were included, with a median (interquartile range) age (years) and weight (kg) of 2 (1-7) and 12.5 (8.9-23.8). Late AKI was identified in 12.6% (21/167). A higher percentage of late AKI patients received concomitant treatment with intravenous acyclovir, amphotericin products, or piperacillin-tazobactam. Age <1 year was the only factor independently associated with late AKI development (odds ratio = 4.4; 95% confidence interval = 1.3-15.4). Conclusions: Late AKI occurred in nearly 13% of children receiving ≥8 days of vancomycin therapy. This study suggests that vancomycin trough concentrations are not associated with late AKI, but that age <1 year and concomitant administration of certain nephrotoxins may be factors associated with increased risk.

show abstract

“…Recent evidence and recommendations suggest that such doses are unlikely to achieve the goal serum trough concentrations (10-20 mg/L) that are necessary for the optimal area under the curve (AUC) for plasma concentration relative to the organism minimum inhibitory concentration (MIC) (AUC/MIC) [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within the First 7 Days of Therapy Associated With Acute Kidney Injury in Children?

Knoderer

Nichols

Lyon

et al. 2013

Journal of the Pediatric Infectious Diseases Society

View full text Add to dashboard Cite

Background. In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development.Methods. Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic fibrosis, an elevated baseline serum creatinine, or without a serum creatinine concentration obtained after receipt of vancomycin were excluded. Acute kidney injury was defined using adapted pediatric RIFLE criteria as an increase in serum creatinine from baseline of 50% or more. BACKGROUNDVancomycin is commonly used in the pediatric population for empiric or targeted treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections and has been associated with acute kidney injury (AKI) [1].Empiric intravenous (IV) vancomycin in children has traditionally been dosed as 40 mg/kg per day in 4 divided doses to achieve target serum trough concentrations of 5-10 mg/L. Recent evidence and recommendations suggest that such doses are unlikely to achieve the goal serum trough concentrations (10-20 mg/L) that are necessary for the optimal area under the curve (AUC) for plasma concentration relative to the organism minimum inhibitory concentration (MIC) (AUC/MIC) [2][3][4][5].

show abstract

Impact of a Hospitalwide Increase in Empiric Pediatric Vancomycin Dosing on Initial Trough Concentrations

Cited by 46 publications

References 17 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

Late-Occurring Vancomycin-Associated Acute Kidney Injury in Children Receiving Prolonged Therapy

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within the First 7 Days of Therapy Associated With Acute Kidney Injury in Children?

Contact Info

Product

Resources

About