Evaluation of Vancomycin Dosing Regimens in Preterm and Term Neonates Using Monte Carlo Simulations

Mehrotra, Nitin; Tang, Lisa; Phelps, Stephanie J.; Meibohm, Bernd

doi:10.1002/j.1875-9114.2012.01029.x

Cited by 49 publications

(53 citation statements)

References 23 publications

(42 reference statements)

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“…access. Our study observed vancomycin pharmacokinetic parameters similar to those of previous studies in neonates (6,18,32). Birth weight (kg) and PNA (days) were identified as significant predictors of vancomycin V in this study.…”

Section: Fig 1 Scatterplots Of Individual Patient Predicted (Based Onsupporting

confidence: 87%

“…In a recent population pharmacokinetic analysis of 214 neonates, significant covariates of vancomycin CL were found to be weight at the time of vancomycin initiation, CGA, and renal function (47). CGA has been considered to be a better predictor of clearance than gestational age or PNA alone, as CGA is highly correlated to weight and physiological maturation of renal function (8,18). However, CGA was not identified as a significant covariate of vancomycin CL in our population, most likely due to the small variability in gestational ages in our study.…”

Section: Fig 1 Scatterplots Of Individual Patient Predicted (Based Onmentioning

confidence: 99%

“…There is no evidence of correlation between serum vancomycin concentrations and clinical cure, microbiological cure, or nephrotoxicity in neonates (6)(7)(8). However, vancomycin trough concentrations are routinely monitored in neonates, and controversy exists with regard to the optimal target vancomycin trough levels, resulting in numerous different target trough concentration ranges being recommended in the literature for these patients (e.g., 5 to 10 mg/ liter, 5 to 12 mg/liter, 5 to 15 mg/liter, 5 to 20 mg/liter, or 12 to 15 mg/liter) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In addition, the majority of the previous studies describing vancomycin pharmacokinetics in neonates have included small, heterogeneous groups with differing demographics, clinical conditions, lengths of infusion period, serum sampling times, and pharmacokinetic models (1-compartment versus 2-compartment models) (8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

“…These guidelines acknowledge that data in children were limited. Two recent neonatal studies (15,18) assessed higher vancomycin target trough concentrations; however, the results from these studies highlight the continued question regarding appropriate vancomycin dosing in neonates and the lack of data to support practical initial dosing for vancomycin in neonates.…”

mentioning

confidence: 99%

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Determination of Vancomycin Pharmacokinetics in Neonates To Develop Practical Initial Dosing Recommendations

Kim

Walker

Iaboni

et al. 2014

Antimicrob Agents Chemother

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f Variability in neonatal vancomycin pharmacokinetics and the lack of consensus for optimal trough concentrations in neonatal intensive care units pose challenges to dosing vancomycin in neonates. Our objective was to determine vancomycin pharmacokinetics in neonates and evaluate dosing regimens to identify whether practical initial recommendations that targeted trough concentrations most commonly used in neonatal intensive care units could be determined. Fifty neonates who received vancomycin with at least one set of steady-state levels were evaluated retrospectively. Mean pharmacokinetic values were determined using first-order pharmacokinetic equations, and Monte Carlo simulation was used to evaluate initial dosing recommendations for target trough concentrations of 15 to 20 mg/liter, 5 to 20 mg/liter, and <20 mg/liter. Monte Carlo simulation revealed that dosing by mg/kg of body weight was optimal where intermittent dosing of 9 to 12 mg/kg intravenously (i.v.) every 8 h (q8h) had the highest probability of attaining a target trough concentration of 15 to 20 mg/liter. However, continuous infusion with a loading dose of 10 mg/kg followed by 25 to 30 mg/kg per day infused over 24 h had the best overall probability of target attainment. Initial intermittent dosing of 9 to 15 mg/kg i.v. q12h was optimal for target trough concentrations of 5 to 20 mg/liter and <20 mg/ liter. In conclusion, we determined that the practical initial vancomycin dose of 10 mg/kg vancomycin i.v. q12h was optimal for vancomycin trough concentrations of either 5 to 20 mg/liter or <20 mg/liter and that the same initial dose q8h was optimal for target trough concentrations of 15 to 20 mg/liter. However, due to large interpatient vancomycin pharmacokinetic variability in neonates, monitoring of serum concentrations is recommended when trough concentrations between 15 and 20 mg/liter or 5 and 20 mg/liter are desired.

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Section: Fig 1 Scatterplots Of Individual Patient Predicted (Based Onsupporting

confidence: 87%

Section: Fig 1 Scatterplots Of Individual Patient Predicted (Based Onmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Determination of Vancomycin Pharmacokinetics in Neonates To Develop Practical Initial Dosing Recommendations

Kim

Walker

Iaboni

et al. 2014

Antimicrob Agents Chemother

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“…L os recién nacidos (RN), y en particular los prematuros de muy bajo peso de nacimiento (RNPret MBPN), definidos como todos aquellos prematuros menores de 1.500 g ó menores de 32 semanas, tienen un sistema inmunitario inmaduro y son altamente susceptibles a las infecciones por microorganismos grampositivos durante su estadía en una Unidad de Cuidados Intensivos Neonatal (UCIN) 1 . Agentes como Staphylococcus coagulasa negativa (SCN) son los causantes más comunes de sepsis neonatal de inicio tardío en las UCIN; sin embargo, su virulencia es baja y la sepsis fulminante es inusual, ocurriendo sólo en 1% de los casos [2][3][4] .…”

Section: Introductionunclassified

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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Clinical application of vancomycin population pharmacokinetics model in patients with hematological diseases and neutropenia

Lin

Huang

et al. 2021

Biopharm & Drug Disp

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To explore the clinical application of a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases and neutropenia. Patients with hematological diseases and neutropenia were included in the PPK model study.Nonlinear mixed effect modeling approach (NONMEM) was used for model establishment. Monte Carlo simulation was carried out. A total of 74 patients were divided into model group and non-model group for clinical application research. The model group was given the initial dose of 1g q8h, and the non-model group was given 1g q12h as an empiric initial dosage. The follow-up dose adjustments were made according to the concentration results. This two-compartment model showed good stability and accuracy. The first trough concentration (C 0 ) and the compliance rate of the first C 0 were much higher in the model group than that in the non-model group (14.30 � 4.73 μg/ml and 59.38% vs. 8.02 � 2.61 μg/ml, 35.71%). Less patients needed dose adjustments and fewer adjustment times in the model group than those in the non-model group (12.50% and 0.13 � 0.34 times vs. 50.00% and 0.61 � 0.66 times). This suggested that for those patients who had a Creatinine clearance rate (CLCR) ≥ 90 ml/min/1.73 m 2 , the initial dose of 1g q8h may help to reach the target C 0 (10∼20 μg/ml) quickly. It also helped to reduce the times and number of patients who need dose adjustments. Our PPK model of vancomycin in patients with hematologic diseases and neutropenia can be used to shorten the time to reach the target concentration and reduce the number of dose adjustments.Clinical trial registration: Not applicable (Retrospective study).

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Evaluation of Vancomycin Dosing Regimens in Preterm and Term Neonates Using Monte Carlo Simulations

Cited by 49 publications

References 23 publications

Determination of Vancomycin Pharmacokinetics in Neonates To Develop Practical Initial Dosing Recommendations

Determination of Vancomycin Pharmacokinetics in Neonates To Develop Practical Initial Dosing Recommendations

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

Clinical application of vancomycin population pharmacokinetics model in patients with hematological diseases and neutropenia

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