Population Pharmacokinetics and Dosing Regimens Optimization of Ceftazidime in Critically Ill Burn Children
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Ceftazidime concentration
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Patient and parents having notified to the doctor that they refuse data recovery and additional blood sample volume
结局指标
主要结局
Ceftazidime concentration
时间窗: Up to 28 days
6 blood samples
次要结局
- Weight (kg)(Up to 28 days)
- Body temperature (°C)(Up to 28 days)
- Minimum Inhibitory Concentration (MIC) of the suspected or documented pathogen(Day 28 after end of Ceftazidime administration)
- Creatinine clearance(Up to 28 days)
- C Reactive Protein(Up to 28 days)
- Albumin levels(Up to 28 days)
- PELOD-2 score (severity score)(Up to 28 days)
- Percentage of body surface burned(Up to 28 days)
- Relapse(Day 28 after end of Ceftazidime administration)