Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin During Bone and Joint Infections: a Prospective, Randomized, Open-label, Monocentric Crossover Study.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: T> minimal inhibitory concentration
研究概览
简要总结
Our objective is to establish pharmacological equivalence of intermittent and continuous infusion of cloxacillin during methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI). Twelve patients suffering MSSA BJI will receive both administration modalities and serum concentrations of cloxacillin will be determined after 3 days of II and 3 days of continuous infusion in a prospective, randomized, open-label, monocentric crossover study design.
详细描述
Introduction Staphylococcus aureus is the main causative agent of bone and joint infections (BJI). More than 80% of the strains isolated in France are methicillin-susceptible (MSSA). During the early phase of MSSA BJI management national and international guidelines recommend the use of intra-venous type M penicillin with a dosage ranging from 100 to 200 mg/kg/day. Pharmacological properties of this class of penicillin require 4 to 6 infusions by day. Continuous infusion of beta-lactams is increasingly used especially in intensive care units. It allows an improvement of pharmacokinetic/pharmacodynamics (PK/PD) parameters and a reduction in time dedicated to infusion preparations by the nurses. However pharmacological data regarding such administration is required for type M penicillin.
Design A 6-day, prospective, randomized, open-label, monocentric crossover study
Participants Twelve adult patients with MSSA BJI
Intervention Patients will be randomized in two groups: the first group will receive 3 days of cloxacillin (150 mg/kg/day) through 4 intermittent infusions/day followed by 3 days of cloxacillin (150 mg/kg/day) through continuous infusion (2 infusions during 12 hours). In the second group the infusion modalities will be inverted and continuous infusion will be preceded by a loading dose. Serum concentrations of cloxacillin will be determined at Day 3 and Days 6 The area under the curve / minimal inhibitory concentration ratio will be use to establish the equivalence between both administration modalities.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Staphylococcus aureus sensitive to methicillin and to be treated with cloxacillin by injectable antibiotic monotherapy For patients with Osteo-articular infection on material
- •Presence of a fistula in contact with the prosthesis or implant.
- •Pus in the joint or in contact with the prosthesis or implant
- •Presence of at least 1 positive sample (1 sampling by articular puncture or 1 peroperative sampling or by blood culture)
- •A histological analysis of the peri-prosthetic osteo-articular tissue which is the object of acute inflammation is a strong argument in favor of an Osteo-articular infection on material
- •For spondylodiscitis
- •Culture of a disco-vertebral biopsy puncture to isolate a methicillin sensitive S. aureus
- •Positive haemocultures for S. aureus sensitive to methicillin with imaging examination (CT or MRI of the spine) showing images of spondylodiscitis
- •For primitive arthritis :
- •Culture of a positive methicillin-sensitive S. aureus articular fluid puncture
- •Cultivation of a methicillin-sensitive S. aureus-positive surgical joint lavage fluid
- •For osteitis the diagnosis is based on the following criterion:
- •*Culture of surgical specimens from a focal zone of methicillin-sensitive S. aureus-positive osteitis
排除标准
- •Allergy to betalactamines
- •Taking penicillin M within 36 hours before inclusion Renal function impaired with a glomerular filtration rate measured by MDRD formula of less than 30 ml / min
- •Patient with renal function expected to change within 6 days of inclusion
- •Hepatocellular insufficiency, whatever the degree
- •*Methotrexate intake
- •Polytransfused (more than 2 CGR) in the previous week
- •Patients requiring resuscitation
研究组 & 干预措施
Intermittent administration of cloxacillin
干预措施: Modification for administration mode of cloxacillin antibiotic (Drug)
continuous administration of cloxacillin
干预措施: Modification for administration mode of cloxacillin antibiotic (Drug)
结局指标
主要结局
The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: T> minimal inhibitory concentration
时间窗: Six days
The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: the area under the curve (AUC) / minimal inhibitory concentration
时间窗: Six days
次要结局
未报告次要终点