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ANTIBIOTICADOSERING BIJ KRITIEK ZIEKE KINDEREN :

SO YOU THINK YOU CAN PRESCRIBE?

Pieter De Cock , PharmD.

Department of Pharmacy, Ghent University Hospital, Ghent, BEDepartment of Paediatric Intensive Care, Ghent University Hospital, Ghent, BEHeymans Institute of Pharmacology, Ghent University, Ghent, BE

2015

10e PICU THANKSGIVING SYMPOSIUM, HET PAND, GENTCover: Flavie De Cock®

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“een DOELTREFFENDE, VEILIGE en kosteneffectieve

ANTIBIOTICA - therapie verzekeren vanaf

1. het voorschrijven en de

2. bereiding van het geneesmiddel

3. over zijn toediening,

4. tot en met de opvolging van de therapie

–

met respect voor de keuze/wilvan het kind

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Farmaceutische aspecten

Labo parameters

Leeftijd

Micro-organisme

DOSERING ?

• Hoeveel?

• Hoe vaak?

• Hoelang?

• In welke vorm?

Pathologie

Antibiotica eigenschappen

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Leeftijd

Micro-organisme

DOSERING ?

• Hoeveel?

• Hoe vaak?

• Hoelang?

• In welke vorm?

Pathologie

Antibiotica eigenschappen

• ontogenie

Farmaceutische aspecten

Labo parameters

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Leeftijd

Micro-organisme

DOSERING ?

• Hoeveel?

• Hoe vaak?

• Hoelang?

• In welke vorm?

Pathologie

Antibiotica eigenschappen

• resistentie(-patroon)

• inoculum

• ontogenie

Farmaceutische aspecten

Labo parameters

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Leeftijd

Micro-organisme

DOSERING ?

• Hoeveel?

• Hoe vaak?

• Hoelang?

• In welke vorm?

Pathologie

Antibiotica eigenschappen

• resistentie-patroon

• inoculum

• PK – PD

• weefselpenetratie

• ontogenie

Farmaceutische aspecten

Labo parameters

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PK-PD parameter targetsPK-PD parameter targets

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EFFICACYEFFICACY

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Roberts J. et al. Clinical Infectious Diseases 2014;58:1072-1083

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TOXICITYTOXICITY

J Pediatric Infect Dis Soc. 2015 Dec;4(4):e109-16. doi: 10.1093/jpids/piu110.

Leeftijd

Micro-organisme

DOSERING ?

• Hoeveel?

• Hoe vaak?

• Hoelang?

• In welke vorm?

Pathologie

Antibiotica eigenschappen

• resistentie-patroon

• inoculum

• PK – PD

• weefselpenetratie

• infectieuze pathologie

• onderliggende pathologie

• ontogenie

Farmaceutische aspecten

Labo parameters

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Boucher BA et al. Pharmacokinetic Changes in Critical Illness. Crit Care Clin 2006 Apr;22(2):255-71, vi

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MECHANISMMECHANISM

Clin Pharmacokinet. 2010;49(1):1-16

INCIDENCE on PICUINCIDENCE on PICU

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Pilot study B. Leenknegt, K. Roelandt, UGent 2014

• Inclusion criteria:- admission to P(C)ICU

- 1 month – 15 year

- with bladder catheter

- no hemodialysis or peritoneal dialysis

• GFR ~Calculated 24 hour creatinin clearance

• Definition hyperfiltration: GFR-normal value (for age) + 2 SD

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No

YES

NO

YES

<1 y 1 y-6 y > 6y

Nu

mb

er

of

pts

.

Implications of augmented renal clearance

on amoxicillin-clavulanic acid dosing

in critically ill children

Pieter De Cock1,2,5, Joseph Standing4, Charlotte Barker4, Annick de Jaeger2, Evelyn Dhont2, Mieke Carlier3, Alain Verstraete3, Joris Delanghe3, Hugo Robays1, Peter De Paepe5

Dpt. of Pharmacy1, Paediatric Intensive Care2, Laboratory Medicine3, Ghent University Hospital, Ghent, BE

London Pharmacometrics Group4, University College London, London, UK

Heymans Institute of Pharmacology5, Ghent University, Ghent, BE

Accepted for publication in Antimicrobial Agents and Chemotherapy 2015

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OBJECTIVES

• To investigate AMC pharmacokinetics in

critically ill infants and children

• To evaluate the efficiency of current and

alternative AMC dosing strategies ~ fT>MIC

MATERIALS AND METHODS

Study design (EC/2012/172) (NCT02456974)

• Single-center, prospective, open-label observational PK study

Inclusion criteria

• Patient age: 1 month-15 years

• Intravenous AMC treatment

• Informed Consent

Exclusion criteria

• Extracorporeal circuit

• No access for blood sampling

Drug dosing and administration

• 25 mg/kg q6h over 5-30 minutes ~hospital dosing guideline 22

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Assessment of dose-exposure relationship

• Monte Carlo simulations (n=1000 patients)

• Target efficacy exposure : 40% fT>MIC 1

• Target MICamoxicillin: 8 mg/L (E. coli EUCAST breakpoint)2 ; target fTclavulanic acid> 2 mg/L2

• Mean protein binding taken into account

1Haeseker M. et al. BMC Pharmacol Toxicol 2014 ; 2European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables

MATERIALS AND METHODS

Dosing regimen Drug Formulary

1-3 months: 25 mg/kg q12h

>3 months: 25 mg/kg q8h

British National Formulary for Children

version 2013-2014

25 mg/kg q6h Sanford Guide

23rd edition of the Belgian-Luxembourg

version 2012-2013

25 mg/kg q4h /

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Demographic, clinical and treatment characteristics

Characteristic Median (range) or No. (%)

Sex

male 30 (60)

female 20 (40)

Age (years) 2.58 (0.08-15)

Weight (kg) 14.4 (4.07-65)

Pediatric Risk of Mortality II score 6.5 (0-32)

Reason for antibiotic treatment

treatment of infection 33 (66)

postoperative prophylaxis 17 (44)

Mechanical ventilation 29 (58)

Vasopressor treatment 16 (32)

Pediatric Logistic Organ Dysfunction score 1 (0-31)

Serum Creatinine (mg/dL) 0.21(<0.17-1.89)

Plasma Cystatin C (mg/L) 0.63 (0.33-1.23)

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RESULTSTarget attainment for ‘typical’ patients (n=1000 simulations)

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RESULTS

Target attainment for the final dose recommendation (n=1000 simulations)

25 mg/kg given 4 hourly

• as a bolus for patients with a cystatin C =>1 mg/L

• as a 1 hour infusion for cystatin C below 1 mg/L

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Antibiotica eigenschappenLeeftijd

Micro-organisme

• IV access

• compatibiliteit

• medicatiefouten

• oplosbaarheid

• stabiliteit

• smaak

• resistentie-patroon

• inoculum

• PK – PD

• weefselpenetratie

DOSERING ?

• Hoeveel?

• Hoe vaak?

• Hoelang?

• In welke vorm?

Pathologie

• infectieuze pathologie

• onderliggende pathologie

• ontogenie

Farmaceutische aspecten

Labo parameters

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30Bron: Wetenschappelijke bijsluiter Augmentin

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ANTIBIOTICADOSERING BIJ KRITIEK ZIEKE KINDEREN :

NOBODY REALLY KNOWS, BUT THE SUN IS RISING

Pieter De Cock , PharmD.

Department of Pharmacy, Ghent University Hospital, Ghent, BEDepartment of Paediatric Intensive Care, Ghent University Hospital, Ghent, BEHeymans Institute of Pharmacology, Ghent University, Ghent, BE

2015

10e PICU THANKSGIVING SYMPOSIUM, HET PAND, GENTCover: Flavie De Cock®

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• Ghent University Hospital Research Fund

• Neonatal and Paediatric Intensive Care Unit, Ghent University Hospital, Belgium

• medical and nursing staff

• Paediatric Intensive Care Unit,Hôpital Reine Fabiola, Brussels, Belgium

• Dr. Dominique Biarent

• Barbara Van De Goor

• SAFEPEDRUG Consortium safepedrug.eu, Belgium

• Prof. Johan Vande Walle

• Prof. Peter De Paepe

• Apr. Sarah Desmet

• Study nurse team (Daphne Christiaens, Alien Verbeke, Fien De Wolf)

ACKNOWLEDGEMENTS

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