Ceftazidime in Burn Children
Condition: Burned Children; Ceftazidime Treatment
MeSH terms: Burns
Study type: Observational

Summary: 
      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: 
      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
    

Intervention name(s): titration- blood sample
Intervention type(s): Other
Intervention description(s): Ceftazidime titration
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Burned children requiring the administration of Ceftazidime for the treatment of a
        documented or suspected bacterial infection
      
Keywords: Ceftazidime; Burned Children; Intensive care; Pharmacokinetic