Dataset Information

Assessment of Vancomycin Pharmacokinetics and Dose Regimen Optimisation in Preterm Neonates.

ABSTRACT:

Background

The pharmacokinetics of vancomycin, a drug used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), varies between paediatric and adult patients.

Objective

The objective of this study was to assess the pharmacokinetics of vancomycin in preterm neonates and determine the optimum dose regimen.

Methods

This was a randomised double-blind study of preterm neonates admitted to neonatal intensive care units. They all received vancomycin 15 mg/kg every 12 h. Blood was sampled just before administration of the third, sixth and ninth vancomycin dose. Pharmacokinetic parameters were estimated using a Bayesian approach implemented in Monolix 2018R2 software. Covariates assessed included postmenstrual age, current weight, creatinine clearance, albumin, gestational age, body surface area and current age. We used Monte Carlo simulations for dose regimen optimisation targeting area under the concentration-time curve up to 24 h (AUC_0-24h) of ??400 mg?×?h/L.

Results

In total, 19 preterm neonates were enrolled in the study with a median age of 14 (3-58) days. A one-compartment model with linear elimination best described the pharmacokinetics of vancomycin. Volume of distribution and clearance was 0.88 L and 0.1 L/h, respectively, for a typical neonate weighing 1.48 kg. Simulation of the current dose regimen showed that 27.5% of the neonates would achieve the target AUC_0-24h of ??400 mg?×?h/L, and 70.7% of the neonates would achieve it with 12 mg/kg every 8 h.

Conclusion

The majority of the neonates were under dosed. Vancomycin 12 mg/kg should be administered every 8 h over 1 h infusion to improve the likelihood of achieving the AUC_0-24h target of ??400 mg?×?h/L. This target is considered optimal for MRSA infections, where the vancomycin minimum inhibitory concentration is ??1 µg/mL.

SUBMITTER: Mulubwa M

PROVIDER: S-EPMC7221111 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Assessment of Vancomycin Pharmacokinetics and Dose Regimen Optimisation in Preterm Neonates.

Mulubwa Mwila M Griesel Heletje Aletta HA Mugabo Pierre P Dippenaar Ricky R van Wyk Lizelle L

Drugs in R&D 20200601 2

<h4>Background</h4>The pharmacokinetics of vancomycin, a drug used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), varies between paediatric and adult patients.<h4>Objective</h4>The objective of this study was to assess the pharmacokinetics of vancomycin in preterm neonates and determine the optimum dose regimen.<h4>Methods</h4>This was a randomised double-blind study of preterm neonates admitted to neonatal intensive care units. They all received vancomycin 15 mg/kg eve ...[more]

PMID: 32266599

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Project description:BackgroundParenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil-containing lipid emulsions.ObjectiveThe aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content.DesignWe conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial.ResultsWe randomly assigned 168 infants born at <31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for nonadipose mass [adjusted mean difference: 1.0 g (95% CI: -108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations >7 mmol/L or >10 mmol/L, respectively (75% compared with 49%, P < 0.01; 49% compared with 18%, P < 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: -0.8 cm (95% CI: -1.5, -0.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes.ConclusionImm-RDI of parenteral amino acids does not benefit body composition or growth to term and may be harmful. This trial was registered at www.isrctn.com as ISRCTN29665319 and at eudract.ema.europa.eu as EudraCT 2009-016731-34.

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Dataset Information

Assessment of Vancomycin Pharmacokinetics and Dose Regimen Optimisation in Preterm Neonates.

Background

Objective

Methods

Results

Conclusion

Publications

Assessment of Vancomycin Pharmacokinetics and Dose Regimen Optimisation in Preterm Neonates.

Similar Datasets

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