Ceftazidime in Burn Children

Study Overview
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Brief Summary
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Concentrations and effects of Ceftazidime in critically ill burn children are unpredictable and the risk of under-exposure may be associated with poor clinical outcomes. In addition, between-subject variability (BSV) is known to be substantial in critically ill burn children. Optimization of Ceftazidime dosing is therefore desirable for all. The investigators aim to investigate, using a population approach, the pharmacokinetics (PK) of Ceftazidime including PK/pharmacodynamic (PD) targets (fT(%) > minimal inhibitory concentration (MIC)) and PD endpoints (clinical outcomes) in critically ill burn children. The effects of covariates on Ceftazidime PK and PK/PDs are investigated in order to better explain the BSV and to ultimately suggest individualized dosage regimens. It will be a prospective PK study. Six blood samples were taken from each patient during dosing interval. The primary PK/ PD targets were Ceftazidime concentrations above the MIC of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. The investigators used skewed logistic regression to describe the effect of Ceftazidime exposure on patient outcome.

Detailed Description
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Background and aims of the study: Recent studies have suggested a risk of under-exposure to anti-infectives in critically ill adults. This under-exposure may be associated with poor clinical outcomes as well as a delay or incomplete clinical resolution of infection; The dosing regimen of anti-infectives in critically ill children is usually based on weight (i.e. mg per Kg). However, between-subject variability is known to be substantial in children and even more so with burns and in critical illness. Ceftazidime is one of the most anti-infective agents used in this vulnerable population. Given to the expected high BSV, concentrations and effects of Ceftazidime are unpredictable and the risk of under exposure- is thus considerable. Rationalization of Ceftazidime in children is therefore desirable. The purpose of the present study is to investigate, using a population approach, the pharmacokinetics (PK) and pharmacodynamics (PD) of Ceftazidime including usual PK/PD targets (fT(%) > minimal inhibitory concentration (MIC)) and PD endpoints (clinical outcomes) in critically ill burn children. The effects of developmental and other factors related to critical illness and burns on Ceftazidime PK and PK/PDs are investigated in order to better explain the observed between-subject variabilities and to ultimately suggest individualized dosage regimens. This prospective study will be conducted in a paediatric intensive care unit of Public Hospitals in Paris, France Intervention: Patient selection will take place in paediatric intensive care unit. The senior physician proposes the study to holders of parental authority whose child receives or will receive Ceftazidime during its follow-up or hospitalization. The senior physician will give a briefing note to the holders of parental authority, and if the child is able to understand the information. The non-oral opposition for the retrieval and analysis of data will be collected. No intervention or no charge will be made for this study

Official Title
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Population Pharmacokinetics and Dosing Regimens Optimization of Ceftazidime in Critically Ill Burn Children

Conditions
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Burned Children, Ceftazidime Treatment

Intervention / Treatment
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* Other: titration- blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age: > 1 month and < 18 years Patient weight > 3 Kg Patient requiring the administration of Ceftazidime for the treatment of a documented or suspected bacterial infection Exclusion Criteria: Patient and parents having notified to the doctor that they refuse data recovery and additional blood sample volume

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: titration- blood sample|Ceftazidime titration|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ceftazidime concentration | 6 blood samples | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight (kg) | Composite measure of the health condition : clinical data | Up to 28 days | 
| Body temperature (°C) | Composite measure of the health condition : clinical data | Up to 28 days | 
| Creatinine clearance | Composite measure of the health condition : biological data | Up to 28 days | 
| Albumin levels | Composite measure of the health condition : biological data | Up to 28 days | 
| PELOD-2 score (severity score) | Composite measure of the health condition : clinical data | Up to 28 days | 
| Percentage of body surface burned | Composite measure of the health condition : clinical data | Up to 28 days | 
| C Reactive Protein | Composite measure of the health condition : biological data | Up to 28 days | 
| Relapse | Composite measure of the health condition | Day 28 after end of Ceftazidime administration | 
| Minimum Inhibitory Concentration (MIC) of the suspected or documented pathogen |  | Day 28 after end of Ceftazidime administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ceftazidime, Burned Children, Intensive care, Pharmacokinetic