Beta-Lactams Dosing In Pneumonia in ICU in Patients Treated by Continuous Renal Replacement Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Percentage of beta-lactams concentrations above plasma therapeutic levels
研究概览
简要总结
Pneumonia are the most frequent infections in ICU. Little is known about beta-lactam doses necessary for this infection for patients treated with continuous veino-veinous hemodialysis. The pharmacokinetic variability expose to over and underdosage leading to toxicity or therapeutic failure. The aim of this study is to define if beta-lactams doses used in pneumonia for patients with acute kidney injury treated with our hemodialysis conditions lead to beta-lactam therapeutic plasma levels.
详细描述
Pneumonia are the most frequent infections in ICU. Little is known about beta-lactam doses necessary for this infection for patients treated with continuous veino-veinous hemodialysis. The pharmacokinetic variability expose to over and underdosage leading to toxicity or therapeutic failure. The aim of this study is to define if beta-lactams doses used in pneumonia for patients with acute kidney injury treated with our hemodialysis conditions lead to beta-lactam therapeutic plasma levels.
This prospective observational multicenter study will include all patients with pneumonia treated by beta-lactam and continuous veino-veinous hemodialysis in 5 ICU. Blood sampling will be done at assumed pharmacokinetic steady state. Protocol sample concentrations of beta-lactams immediately prior to re-dosing, after 24 hours of association of intraveinous beta-lactam and continuous veino-veinous hemodialysis. Another sample will be done after 48 hours. The ICU measured bacterial MICs routinely when the pathogen will be determined. Surveyed ICUs will adopt SFM-EUCAST breakpoints for the targeted (or suspected) bacteria to determine pharmacokinetic/pharmacodynamic targets when a mesured MIC (Minimum inhibitory concentration) is not available. Local hospital antibiogram data can also be used to describe likely pathogen susceptibility. Target attainment is defined as 100% fT> 5 MIC. Due to the long delay to receive therapeutic drug monitoring results, doses could not be ajusted. Factors which could cause concentrations variations will be registered. When neurotoxicity is suspected, a sample will be realized to know beta-lactam concentration and the adverse event will be notified.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years
- •Receiving intraveinous beta-lactam : amoxicillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepime, meropenem, imipenem
- •With AKI defined as any of the following, and treated with Multifiltrate Ci-Ca CVVHD 1000® kit with a dialysis dose of 25 ml/kg/h :
- •Increase in creatininemia ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48 hours
- •Increase in creatininemia ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days
- •Urine volume < 0.5 ml/kg/h for 6 hours
- •Hospitalized in ICU
- •Presence of a catheter to facilitate sample collection
- •With pneumonia defined as any of the following :
- •Chest X-ray pneumonia : opacities, new or progressive infiltrates
- •AND at least one of the following : hyperthermia > 38°C or hypothermia < 36°C with no other explanation ; leukopenia < 4 G/L ou leukocytosis > 12G/L
- •AND at least one of the following : new onset purulent sputum or change in sputum character, new onset or worsening cough or dyspnea or tachypnea, rales or bronchial breathing, lower oxygen saturation/hypoxemia or increase of oxygen needs or respiratory assistance
- •Treated within 24 hours by citrate hemodialysis AND beta-lactam respecting dose and administration conditions of the study :
- •Amoxicillin : loading dose followed immediately by 2g by extended infusion for 4 hours every 8 hours
- •Amoxicillin-clavulanic acid : 2g every 8 hours by intermittent bolus
- •Piperacillin-tazobactam: loading dose followed immediately by 4g/0.5g by continuous infusion every 8 hours (< 80 kg) ou 6 hours (> 80 kg)
- •Cefotaxime: loading dose followed immediately by 2g by continuous infusion every 8 hours Ceftazidime : loading dose followed immediately by 2g by continuous infusion every 8 hours
- •Cefepime: loading dose followed immediately by 2g by continuous infusion every 8 hours
- •Meropenem : loading dose followed immediately by 2g (> 60 kg) ou 1,33g (< 60 kg) by extended infusion for 4 hours every 8 hours
- •Imipenem : loading dose followed immediately by 750 mg (< 80 kg) ou 1g (> 80 kg) by extended infusion for 4 hours every 6 hours In case of extrem weight, dose will be on investigator's discretion but administration conditions have be to respected.
- •No objection has been obtained from the patient or their legally authorised representative
排除标准
- •Aged < 18 years
- •Cystic fibrosis
- •Burn victim
- •Pregnant woman
- •Any rapidly-progressing disease or immediately life-threatening illness
- •Objection from the patients or their legally authorised representative
- •No social security scheme
- •Interruption of antibiotic before samples
- •Patient in prison
结局指标
主要结局
Percentage of beta-lactams concentrations above plasma therapeutic levels
时间窗: Day 3 after start of antibiotic and continuous veino-veinous hemodialysis
We aimed to obtain concentrations over 5 MIC (Minimum inhibitory concentration) for at least 80% of patients.
次要结局
- Incidence of neurotoxicity(Day 7 after start of antibiotic and continuous veino-veinous hemodialysis)
- Trends in beta-lactam concentrations between 2 days(At Day 1 and Day 2)
- Clinical response observed when beta-lactam concentrations achieved 5 MIC(At Day 28 and day 90)
- Distribution of steady state beta-lactam concentrations and their variability(Day 3 after start of antibiotic and continuous veino-veinous hemodialysis)