Therapeutic drug monitoring in neonates

Pauwels, Steven; Allegaert, Karel

doi:10.1136/archdischild-2013-305309

Cited by 46 publications

(44 citation statements)

References 38 publications

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“…Dose modelling software is now available for use in hospitals, with the support of remote software teams. The advantage of these packages is the provision of individualised advice, tailored to a patient's specific PK . Potential disadvantages of adopting this method include the need for experienced staff and the cost of the software (Table ).…”

Section: Discussionmentioning

confidence: 99%

Vancomycin therapeutic drug monitoring in paediatrics

Patel

Lucas

Ryan

et al. 2019

J Paediatrics Child Health

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Aim: Vancomycin guidelines for therapeutic drug monitoring (TDM) aim to maximise efficacy while minimising toxicity and resistance. Vancomycin is effective against Staphylococcus aureus when it achieves area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) > 400. Studies in children have shown that target trough concentrations poorly correlate to AUC/MIC > 400; however, they are used in practice for clinical convenience. This review in paediatric inpatients aims to audit performance against TDM guidelines and consider what changes are needed to optimise vancomycin monitoring. Methods: Vancomycin prescriptions in patients younger than 18 years old were collected over a 15-month period. Primary outcome measures were vancomycin initial dose (mg/kg/day) and the timing and result of first trough concentration (mg/L). Secondary outcome measures were the numbers achieving recommended targets and whether appropriate dose adjustments were made in response to TDM. Results: A total of 133 courses reached the time when TDM should occur. Average patient age was 6.5 years, and the average initial dose was 52.55 mg/kg/day (range 19.05-86.54 mg/kg). Only 25% of courses (n = 34) had a trough concentration measured at the recommended time. The mean trough concentration was 11.6 mg/L (range < 2.0-39.7). Of 40 patients with a low trough concentration, 50% continued without dose adjustment. Conclusion: As shown in the literature, there is a poor correlation between the vancomycin dose given and the trough concentration achieved. Given that recommendations for trough concentration monitoring are designed to simplify the process yet are poorly adhered to, a strategic plan to address these issues is needed.

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Section: Discussionmentioning

confidence: 99%

Vancomycin therapeutic drug monitoring in paediatrics

Patel

Lucas

Ryan

et al. 2019

J Paediatrics Child Health

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“…A patient‐tailored optimized dosing regimen should be routinely used to individualize vancomycin continuous administration . Several authors anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in individualizing therapy in neonates .…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

“…Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may differ in neonates. 55 With currently recommended vancomycin dosing, the therapeutic target of AUC/MIC > 400 is achieved only by 25% of neonates. 56 Most of Ctrough in neonates achieved using two published dosing regimens did not reach the 10 mg/L.…”

Section: (B) Neonatesmentioning

confidence: 99%

“…62 Several authors anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in individualizing therapy in neonates. 55 Modeling and simulation approaches have clear advantages in dosing optimization of antimicrobial agents in neonates. 63 Pharmacometric modeling and simulation approaches allow to characterize population average, pharmacokinetic parameters, intra and intersubject variability, and to identify and quantify key factors that influence antibiotics pharmacokinetic behavior during the neonatal period.…”

Section: (B) Neonatesmentioning

confidence: 99%

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Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Monteiro

Hahn

Gonçalves

et al. 2018

Pharmacology Res & Perspec

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Vancomycin is a fundamental antibiotic in the management of severe Gram‐positive infections. Inappropriate vancomycin dosing is associated with therapeutic failure, bacterial resistance and toxicity. Therapeutic drug monitoring (TDM) is acknowledged as an important part of the vancomycin therapy management, at least in specific patient subpopulations, but implementation in clinical practice has been difficult because there are no consensus and agglutinator documents. The aims of the present work are to present an overview of the current knowledge on vancomycin TDM and population pharmacokinetic (PPK) models relevant to specific patient subpopulations. Based on three published international guidelines (American, Japanese and Chinese) on vancomycin TDM and a bibliographic review on available PPK models for vancomycin in distinct subpopulations, an analysis of evidence was carried out and the current knowledge on this topic was summarized. The results of this work can be useful to redirect research efforts to address the detected knowledge gaps. Currently, TDM of vancomycin presents a moderate level of evidence and practical recommendations with great robustness in neonates, pediatric and patients with renal impairment. However, it is important to investigate in other subpopulations known to present altered vancomycin pharmacokinetics (eg neurosurgical, oncological and cystic fibrosis patients), where evidence is still unsufficient.

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“…Yet successful application of adult or older children pharmacology data to neonates is hampered due to unique developmental physiologic processes, changing body composition, and a nonlinear relationship between growth and development in neonates, which contribute to poor correlation between drug dosage and serum concentrations. 1,[7][8][9][10][11] These developmental changes and, to a lesser extent, genetic variation are important determinants of drug response. The absorption, distribution, metabolism, and elimination of medications are often quantified with PK parameters such as bioavailability, clearance, volume of distribution, and half-life.…”

Section: Why Neonatal Pharmacology Is Uniquementioning

confidence: 99%

Suggestions for Model‐Informed Precision Dosing to Optimize Neonatal Drug Therapy

Euteneuer

Kamatkar

Fukuda

et al. 2018

The Journal of Clinical Pharma

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Evidence for dosing, efficacy, and safety of most medications used to treat neonates is sparse. Thus, dosing is usually derived by extrapolation from adult and pediatric pharmacologic data with scaling by body weight or body surface area. This may lead to drug dosing that is unsafe or ineffective. However, new strategies are being developed and studied to dose medications in critically ill neonates. Mass spectroscopy technology capable of quickly analyzing drug levels is readily available. Software that integrates population pharmacokinetics and pharmacodynamics with data from sparse samples from neonates allows for timely adjustments of dosing to achieve the desired effect while minimizing adverse outcomes. Some genetic polymorphisms that affect drug response in neonates have also been reported. This review highlights aspects of drug response and how it is impacted by prematurity, assesses pharmacogenomic studies in neonates, and offers suggestions for innovative pharmacokinetic/pharmacodynamic model-based approaches that combine population- or physiology-based pharmacology data, Bayesian analysis, and electronic decision support tools for precision dosing in neonates while illustrating examples where this approach can be used to optimize medical therapy in neonates. Barriers to implementing precision dosing in neonates and how to overcome them are also discussed.

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Therapeutic drug monitoring in neonates

Cited by 46 publications

References 38 publications

Vancomycin therapeutic drug monitoring in paediatrics

Vancomycin therapeutic drug monitoring in paediatrics

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Suggestions for Model‐Informed Precision Dosing to Optimize Neonatal Drug Therapy

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