Ceftazidime in Burn Children (CEFTAZOPTIM)

Assistance Publique - Hôpitaux de Paris

Status: Completed

Conditions: Burned Children; Ceftazidime Treatment

Treatments: Other: titration- blood sample

Study type: Observational

Funder types: Other

Identifiers

NCT03881800

2019-A00035-52 (Other Identifier)

APHP180163

Details and patient eligibility

About

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.

Full 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

Enrollment: 3 patients

Sex: All

Ages: 1 month to 18 years old

Volunteers: No Healthy Volunteers

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