Jaya Madhura Parasuraman1, Frank Kloprogge2, Joseph Frank Standing3, Mahableshwar Albur4, Axel Heep5. 1. Neonatal Intensive Care Unit, Southmead Hospital, Southmead Road, Bristol, United Kingdom, BS10 5NB; Infection, Inflammation and Rheumatology Section, Institute of Child Health, University College London, 30 Guilford Street, Holborn, London, United Kingdom, WC1N 1EH. Electronic address: Jaya.Parasuraman@nbt.nhs.uk. 2. Institute for Global Health, University College London, 30 Guilford Street, Holborn, London, United Kingdom, WC1N 1EH. 3. Infection, Inflammation and Rheumatology Section, Institute of Child Health, University College London, 30 Guilford Street, Holborn, London, United Kingdom, WC1N 1EH. 4. Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol, United Kingdom, BS10 5NB. 5. Neonatal Intensive Care Unit, Southmead Hospital, Southmead Road, Bristol, United Kingdom, BS10 5NB; Neonatal Neurology Group, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom, BS8 1TH.
Abstract
AIM: Intraventricular vancomycin is an effective treatment for neonatal ventriculitis, as the cerebrospinal fluid (CSF) vancomycin levels reach adequate concentrations to achieve microbiological cure. There is no robust data on intraventricular vancomycin pharmacokinetics in the preterm population. This pilot population pharmacokinetic modelling study examines the pharmacokinetic behaviour of intraventricular vancomycin in the preterm population of < 28 weeks gestation, to inform the feasibility of future prospective studies. METHODS: The study comprised 8 preterm infants with neonatal ventriculitis (median gestation age 25.3 weeks; range 23.9 - 27.7). Population pharmacokinetics (non-linear mixed effects modelling) were described with one- and two-compartment models to fit plasma concentrations of vancomycin. A CSF compartment was added to the plasma modelling and mass transfer examined. Three covariates (serum creatinine, ventricular index (VI) and CSF protein) were tested on the final model. Area under the curve (AUC) and average CSF concentration (C average) predictions were generated from the final model and compared with time to microbiological cure. RESULTS: A one-compartment model provided the best fit to the data. There was no appreciable transfer between plasma and CSF. None of the covariates provided a significant reduction in the objective function value (OFV). Generally, time to sterilisation with higher CSF AUC (0-24) and C average tends to be shorter, however this should be interpreted with caution as data is erratic. CONCLUSION: This pilot population pharmacokinetic analysis provides important information to warrant changes in the management of intraventricular vancomycin treatment in the preterm population, such as the current use of VI as a dosing parameter. Further study with a larger data pool is necessary to investigate the influence of VI on CSF vancomycin and ascertain dosing strategies.
AIM: Intraventricular vancomycin is an effective treatment for neonatal ventriculitis, as the cerebrospinal fluid (CSF) vancomycin levels reach adequate concentrations to achieve microbiological cure. There is no robust data on intraventricular vancomycin pharmacokinetics in the preterm population. This pilot population pharmacokinetic modelling study examines the pharmacokinetic behaviour of intraventricular vancomycin in the preterm population of < 28 weeks gestation, to inform the feasibility of future prospective studies. METHODS: The study comprised 8 preterm infants with neonatal ventriculitis (median gestation age 25.3 weeks; range 23.9 - 27.7). Population pharmacokinetics (non-linear mixed effects modelling) were described with one- and two-compartment models to fit plasma concentrations of vancomycin. A CSF compartment was added to the plasma modelling and mass transfer examined. Three covariates (serum creatinine, ventricular index (VI) and CSF protein) were tested on the final model. Area under the curve (AUC) and averageCSF concentration (C average) predictions were generated from the final model and compared with time to microbiological cure. RESULTS: A one-compartment model provided the best fit to the data. There was no appreciable transfer between plasma and CSF. None of the covariates provided a significant reduction in the objective function value (OFV). Generally, time to sterilisation with higher CSF AUC (0-24) and C average tends to be shorter, however this should be interpreted with caution as data is erratic. CONCLUSION: This pilot population pharmacokinetic analysis provides important information to warrant changes in the management of intraventricular vancomycin treatment in the preterm population, such as the current use of VI as a dosing parameter. Further study with a larger data pool is necessary to investigate the influence of VI on CSFvancomycin and ascertain dosing strategies.
Authors: Pieter A J G De Cock; Sarah Desmet; Annick De Jaeger; Dominique Biarent; Evelyn Dhont; Ingrid Herck; Daphné Vens; Sofie Colman; Veronique Stove; Sabrina Commeyne; Johan Vande Walle; Peter De Paepe Journal: J Antimicrob Chemother Date: 2017-03-01 Impact factor: 5.790
Authors: Eva Germovsek; Alison Kent; Tuuli Metsvaht; Irja Lutsar; Nigel Klein; Mark A Turner; Mike Sharland; Elisabet I Nielsen; Paul T Heath; Joseph F Standing Journal: Antimicrob Agents Chemother Date: 2016-07-22 Impact factor: 5.191