The Population Pharmacokinetics Study of Tigecycline and Pharmacokinetics- Pharmacodynamics Index in Patients With Carbapenem Resistant Enterobacteriaceae Bloodstream Infection
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- rate constant for tigecycline distribution from the peripheral to central the compartment
研究概览
简要总结
Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent global public health problem. Patients who were infected caused by CRE bloodstream infection were high mortality up to 40%. The National Antimicrobial Resistance Surveillance Center, Thailand (NARST) reported CRE increased from 1.1% to 17.9%. For carbapenemase producing CRE in Thailand was reported blaNDM 47.33%, blaOXA-48 43.33% and blaNDM+blaOXA-48 6.67%.
Tigecycline (TGC) was a glycylcyclines antibiotics. High dose tigecycline (HD-TGC) loading dose 200 mg then TGC 100 mg q 12 h via intravenous improve clinical cure in critically ill patients and reduce mortality in carbapenem resistance Klebsiella pneumoniae bloodstream infection compared with standard dose therapy. TGC has susceptibility to CR-KP 79.6% and has an activity to blaNDM, blaKPC and blaOXA-48 carbapenemase producing CRE. However, TGC has clearance (CL) 0.2-0.3 L/h/kg, and high volume of distribution (vd) 2.8-13 L/kg resulted in low levels of TGC in plasma. Moreover, the pharmacokinetics of TGC in critically ill was limited and inconsistent with the previous study. Now pharmacokinetics-pharmacodynamics index (PK/PD index) of TGC for CRE bloodstream infection was not reported. This study aims to study the population pharmacokinetic and PK-PD index of TGC in patients who were CRE bloodstream infection to increase the success rate of treatment.
详细描述
Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent global public health problem. Patients who were infected caused by CRE bloodstream infection were high mortality up to 40%. The National Antimicrobial Resistance Surveillance Center, Thailand (NARST) reported the carbapenem resistance Klebsiella pneumoniae (CR-KP) prevalence increased from 1.1% in 2000 to 17.9% in 2021 and the carbapenem resistance Escherichia coli was increased from 0.6% in 2000 to 5% in 2021. For carbapenemase producing CRE in Thailand was reported blaNDM 47.33%, blaOXA-48 43.33%, and blaNDM+blaOXA-48 6.67%. Ceftazidime-avibactam was first-line of treatment for CRE bloodstream infection recommended by Infectious Disease Society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections but ceftazidime-avibactam was limited activity to blaNDM carbapenemase producing CRE.
Tigecycline (TGC) was a glycylcyclines antibiotics. TGC was approved for U.S.FDA for complicated intra-abdominal infection, complicated skin and skin structure infection and community acquired pneumonia with loading dose TGC 100 mg then TGC 50 mg q 12 h via intravenous. High dose tigecycline (HD-TGC) loading dose 200 mg then TGC 100 mg q 12 h improve clinical cure in critically ill patients and reduce mortality in CR-KP bloodstream infection compared with standard dose therapy. TGC has susceptibility to CR-KP 79.6% and has an activity to blaNDM, blaKPC and blaOXA-48 carbapenemase producing CRE. However, TGC has clearance (CL) 0.2-0.3 L/h/kg, and high volume of distribution (vd) 2.8-13 L/kg resulted in low levels of TGC in plasma. Moreover, the pharmacokinetics of TGC in critically ill was limited and inconsistent with the previous study. Now pharmacokinetics-pharmacodynamics index (PK/PD index) of TGC for CRE bloodstream infection was not reported. This study aims to study the population pharmacokinetic and PK-PD index of TGC in patients who were CRE bloodstream infection to increase the success rate of treatment.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •20 years and older who were admitted at Phramongkutklao Hospital
- •Patients who were diagnosed bloodstream infection with CRE and who were sepsis or septic shock
- •Patients who received tigecycline loading dose 200 mg infusion for 1 hour and following maintenance dose 100 mg every 12 h infusion for 1 hour at least 48 hours and grant for blood collection
排除标准
- •Pregnancy or Breastfeeding
- •Patients who cannot tolerant to the toxicity of tigecycline for example hypersensitivity to tigecycline or any component of the formulation
- •Patients who were infected with more than one isolated in blood culture at the same time
结局指标
主要结局
rate constant for tigecycline distribution from the peripheral to central the compartment
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
steady state volume distribution
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
Area under the plasma concentration versus time curve (AUC)
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
Peak Plasma Concentration (Cmax)
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
total clearance
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
elimination rate constant
时间窗: up to 6 months
Population pharmacokinetic parameter of tigecycline
volume of central compartment
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
rate constant for tigecycline distribution from the central to the peripheral compartment
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
intercompartmental clearance
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
volume distribution of peripheral compartment
时间窗: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
次要结局
- PK/PD index for CRE bloodstream infection(up to 6 months)
- Number of Participants with the microbiological outcome(7 days)
- Number of Participants with the clinical outcome(14 days)
- Rate of mortality(7,14 and 28 days)
- Genotype classification of carbapenemase producing CRE(up to 6 months)