Study of the Pharmacokinetics of Ceftriaxone in Urinary Tract Infections in the Emergency Department
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Proportion of patients with urinary tract infection (UTI) for whom the time spent with a free ceftriaxone concentration
研究概览
简要总结
Urinary tract infections (UTIs) are the leading cause of community-acquired bacterial infections in adults. They are a common reason for admission to the Emergency Department (ED), particularly when pyelonephritis is suspected. The main bacteria responsible for UTIs are Enterobacteriaceae, with Escherichia coli being the main cause, found in more than 90% of cases. The French guidelines of the SPLIF (French-Speaking Infectious Pathology Society) recommend the probabilistic use of a 3rd generation cephalosporin or a fluoroquinolone. Ceftriaxone is often chosen over cefotaxime because it can be injected only once a day, which simplifies its administration in overcrowded emergency departments. There are currently no SPLIF recommendations regarding the dosage of ceftriaxone to be administered. The IDSA (Infectious Diseases Society of America) suggests a single dosage of 1 gram/day. Ceftriaxone is a 3rd generation cephalosporin antibiotic in the β-lactam class. Its mechanism of action is based on the inhibition of bacterial cell wall synthesis. Due to its broad spectrum against Gram-positive and Gram-negative aerobic bacteria and also some anaerobic germs, ceftriaxone is a commonly prescribed antibiotic in emergency departments (Therapeutic Guidelines Limited, Melbourne, 2014; Kumar et al., 2009) because of its broad indications: neuromeningeal infections, intra-abdominal infections and urinary tract infections (UTIs). Since most UTIs requiring hospitalization do not require intensive care, the optimal dosage of ceftriaxone in this context remains to be determined. Indeed, patients in emergency departments are on average less serious, without sepsis or septic shock, and therefore with probably different pharmacokinetic parameters.
详细描述
While PK data in healthy volunteers support a single dose of ceftriaxone 1 gram/day, those from intensive care patients support 2 or even 4 grams/day. Febrile UTIs are a heterogeneous group of patients ranging from simple acute pyelonephritis in young women with no history to complex urinary tract infection in malnourished elderly patients and male urinary tract infection in elderly patients with benign prostatic hyperplasia. The present project therefore aims to evaluate whether a single dose of 1 g of ceftriaxone is sufficient to achieve the therapeutic target in all patients suffering from febrile UTI without septic shock or whether certain situations would justify a dosage adjustment. To this end, patients presenting a clinical and biological picture of UTI and having received ceftriaxone administration will be offered inclusion in this protocol. A 4 mL dry tube and a 4 mL heparinized tube will be collected for the determination of total and free ceftriaxone, albumin, and bilirubin concentrations. These samples will be added to the assessment performed as part of routine care within 24 hours of the first ceftriaxone injection. This study will calculate the probability of reaching the therapeutic target in patients treated with ceftriaxone for UTI without septic shock. Depending on the results, this study could allow the proposal of a personalized dosage of ceftriaxone for each patient suffering from urinary tract infection based on their clinical and biological parameters.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 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
- •Adult patient over 18 years of age
- •Requiring hospitalization at Rouen University Hospital
- •Clinical diagnosis of urinary tract infection requiring ceftriaxone antibiotic therapy
- •Prescription of 1g IV ceftriaxone
- •Venipuncture for laboratory testing as part of the prescribed treatment within 24 hours of the first ceftriaxone injection
- •Patient has read and understood the information letter and given oral consent to participate in the study
排除标准
- •Minor patient
- •Patient hospitalized in an intensive care unit
- •Patient with septic shock
- •Chronic dialysis or indication for emergency renal replacement therapy (ERP)
- •Prescription of a dosage other than 1g intravenously per 24 hours
- •Patient having received more than one injection of 1g ceftriaxone
- •Pregnant, parturient, or breastfeeding woman
- •Person deprived of liberty by an administrative or judicial decision
- •Person placed under judicial protection, guardianship, or curatorship
结局指标
主要结局
Proportion of patients with urinary tract infection (UTI) for whom the time spent with a free ceftriaxone concentration
时间窗: within 24 hours after enrollment visit
To determine the proportion of patients with UTI for whom the time spent with a free ceftriaxone concentration above 1x MIC is 100% (fT \> 1x MIC = 100%). The primary objective will be evaluated by simulation using a two-compartment population pharmacokinetic model whose initial parameters will be set in accordance with the scientific literature. The residual concentration of free ceftriaxone will be used and compared to the critical concentration threshold of ceftriaxone for each pathogen defined by EUCAST (European Committee on Antimicrobial Susceptibility Testing).
次要结局
- Determine a mathematical function allowing the free plasma fraction of ceftriaxone to be extrapolated from the total ceftriaxone concentration(within 24 hours after enrollment visit)
- Determine the probability of reaching the efficiency threshold fT > 1x MIC = 100% for MICs varying from 0.25 to 32 mg/L(within 24 hours after enrollment visit)
- Describe the microbial epidemiology of UTIs in the Emergency Department (ED)(within 24 hours after enrollment visit)
- Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (weight)(within 24 hours after enrollment visit)
- Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (albuminemia)(within 24 hours after enrollment visit)
- Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (bilirubinemia)(within 24 hours after enrollment visit)
- Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (creatinineemia)(within 24 hours after enrollment visit)