Emmanuel Roilides

BackgroundAlthough glycopeptides are among the most commonly used antimicrobials in neonates with suspected late-onset sepsis, little is known about the pharmacokinetics (PK) of teicoplanin in term and preterm neonates. We aimed to develop a population pharmacokinetic model in order to evaluate currently recommended dosing regimen.MethodsBy using D-Optimal design approach, a sparse PK study was designed and implemented in 60 neonates with post-menstrual age (PMA) of 26-43wks. Dosing regimen: loading dose 16mg/kg, maintenance dose 8mg/kg once daily (i.v. 30min infusion). Four blood samples per neonate were collected. Concentrations were quantified by high-pressure liquid chromatographyu2013mass spectrometry. Population PK analysis was performed using NONMEM software. Final PK model was validated by nonparametric bootstrapping and visual predictive check and Monte-Carlo (MC) simulation were performed.ResultsThe covariate model used was CL=0.0234(WT/1765)0.75 L/h ,V1=0.287(/1765) L, Q=0.159(WT/1765)0.75 L/h, V2=0.515(WT/1765) L, while CRCL was also found to be a significant covariate on CL, it was removed for the MC simulations. Inter-individual variability on clearance (CL), central volume (V1), peripheral volume (V2) was 40%, 47%, 51.2%. MC simulation demonstrated that with dose of 8 mg/kg: 81.6% of neonates with weight (WT)1kg versus 89.6%, 95.1% and 97% of neonates with WT: 1-2kg, 2-3kg, u22654kg, respectively reach the Ctrough(120h)15mg/L. Increase in dose at 12mg/kg results in 93.5% of neonates with WT1kg achieving Ctrough(120h)15mg/L. Respective results were found with the use of AUC/MIC>400 as a target.ConclusionsTeicoplanin population PK is variable in neonates with weight having the most significant impact on pharmacokinetics. Based on MC simulation ELBW and VLBW neonates need higher doses especially for Staphylococcus spp. with MICu22651.

Is It Time For A Different Dosing Regimen?

Population Pharmacokinetics Of Teicoplanin In Preterm And Term Neonates

Andrew Pollard

Mary Ramsay

Mike Sharland

Adam Finn

Fernanda Rodrigues

Steve Tomlin

Andrew Cant

Jim Gray

Graham Davies

David Elliman

Karina Butler

Ron Dagan

Ronald de Groot

Susanna Esposito

Manolis Galanakis

Carlo Giaquinto

Paul Heath

Terho Heikkinen

Ulrich Heininger

Philipp Henneke

Irja Lutsar

Hermione Lyall

Federico Martinon Torres

Andrew Riordan

Pablo Rojo

Delane Shingadia

Maria Tsolia

Infectious diseases remain a leading cause of child morbidity and mortality worldwide. Now in its fourth edition, Manual of Childhood Infections is a simple-to-use, evidence-based, and practical handbook on how to recognize, investigate, and manage both common and rare infectious diseases in children and babies. Endorsed by the Royal College of Paediatrics and Child Health and the European Society for Paediatric Infectious Diseases, this fully updated version of the established 'Blue Book' complements the Pan European initiatives and UK diploma courses to harmonise patient management and training in Paediatric Infectious Diseases (PID), making it essential reading for UK and European paediatricians. Manual of Childhood Infections is divided into two alphabetized sections for easy access to information, covering key diagnosis and management features of infections alongside crucial points of epidemiology and clinical features. This fourth edition forms practical reading for practising paediatricians, featuring updates to all key chapters based on a literature review alongside new chapters focusing on emerging problems for Europe.

The Blue Book

Manual of Childhood Infections

Emmanuel Roilides

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