Plasma Concentrations of Amoxicillin Administered in High-doses During the First Week of Treatment : Intra- and Inter-individual Variability, Factors Associated With Overdose and Adverse Events
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 142
- 试验地点
- 2
- 主要终点
- Residual plasma concentrations of administered in high doses amoxicillin
研究概览
简要总结
Amoxicillin is the most prescribed antibiotic in France. High dose intravenous amoxicillin, (dosage greater than or equal to 150 mg / kg / day or 12 g per day for patients over 80 kg) is used in the treatment, in particular, of infectious streptococcal endocarditis. oral, streptococci gallolyticus and enterococci, infections of the central nervous system with sensitive germs including Streptococcus pneumoniae and Listeria monocytogenes, osteo articular infections. The dose-related adverse effects of this antibiotic are nephrological (crystalluria may lead to acute renal failure) and neurologic. Recently, the number of amoxicillin crystalluria reported to pharmacovigilance centers has increased, having led the National Agency of drug and health products safety (ANSM) to recommend the determination of the residual level of amoxicillin during the first week of treatment of these patients. Nevertheless, there is no precise therapeutic target in patients treated with high dose amoxicillin except in the context of critical care. The authors suggest the interest of a target between 4 and 10 times the minimum inhibitory concentration (MIC) based on in vitro efficacy studies, and retrospective observations of toxicity cases.
详细描述
Patients will be followed for 8 days. After inclusion, (day of the introduction of high-dose amoxicillin treatment), the residual amoxicillin plasma concentrations will be determined at Day1, Day4 +/- 1 day and Day7 +/- 1 day of the start of treatment. A urine collection will be performed the same day to search for crystalluria and measure the pH and urinary density.
In case of KDIGO (Kidney Disease Improving Global Outcomes) 2 or 3 stage renal failure or neurological signs compatible with overdose, residual amoxicillin and crystalluria and urinary density and urinary pH will be measured during the day of discovery of renal failure.
In the case of KDIGO stage 1 kidney failure, a residual level of amoxicillin and a crystalluria search and the measurement of urinary density and urinary pH will be carried out the following day, when serum creatinine is checked according to usual practices.
At day 7 the clinical and infectious biological evolution of the patient will be collected.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Major patient, male or female, who has a bacterial infection requiring high dose intravenous amoxicillin antibiotic therapy (greater than or equal to 150 mg / kg / day with a maximum of 12 grams per day or 12 grams per day for patients over 80 kg), according to ANSM recommendations.
- •Able to provide informed consent to participate.
- •Covered by a Social Security scheme.
排除标准
- •Pregnant, breastfeeding, or likely to be pregnant women and in the absence of a negative pregnancy test (blood HCG beta).
- •Patients under guardianship, curatorship, deprived of liberties or subject to a safeguard of justice.
- •Septic shock justifying treatment with pressurized amines.
- •Patient under ventilatory or circulatory support.
- •Patients on dialysis at Baseline or with a creatinin clearance less than or equal to 30mL / min
- •Refusal of participation
- •Hypersensitivity to the active substance, to penicillins. History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam (e.g. cephalosporin, carbapenem or monobactam)
研究组 & 干预措施
Patient reveiving amoxycillin
all patient included in this study
干预措施: Amoxicillin (Drug)
结局指标
主要结局
Residual plasma concentrations of administered in high doses amoxicillin
时间窗: Day 1
research of Residual plasma concentrations of amoxicillin
Residual plasma concentrations of administered in high doses amoxicillin
时间窗: Day 7
research of Residual plasma concentrations of amoxicillin
Residual plasma concentrations of administered in high doses amoxicillin
时间窗: Day 4
research of Residual plasma concentrations of amoxicillin
次要结局
- encephalitic signs(Day 7)
- proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)(day 1)
- epilepsy(Day 7)
- search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition(Day 1)
- confusional state(Day 7)
- renal function impairment during treatment(Day 7)
- age associated with evolution of amoxicillin plasma concentrations(Day 0)
- density of urines in g/mL(Day 1)
- pH of urines(Day 1)
- body mass index associated with evolution of amoxicillin plasma concentrations(Day 0)
- renal function at treatment initiation associated with evolution of amoxicillin plasma concentrations(Day 0)
- germ involved(Day 0)
- MIC of germ(Day 0)
- site of infection(Day 0)
- confusional state(Day 4)
- encephalitic signs(Day 1)
- search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition(Day 7)
- search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition(Day 4)
- proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)(day 7)
- proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)(day 4)
- density of urines in g/mL(Day 7)
- pH of urines(Day 7)
- density of urines in g/mL(Day 4)
- pH of urines(Day 4)
- confusional state(Day 1)
- encephalitic signs(Day 4)
- epilepsy(Day 1)
- epilepsy(Day 4)
- renal function impairment during treatment(Day 1)
- renal function impairment during treatment(Day 4)