Impact of a TDM-guided ECPA Program for Optimizing Pharmacodynamic Target Attainment of Continuous Infusion Beta-lactam-based Regimen on Clinical Outcome in Orthotopic Liver Transplant Recipients With Documented Gram-negative Infections
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
- Verify if the attainment of optimal beta-lactam PK/PD targets improves the rate of clinical cure in OLT recipients with documented Gram-negative infections
研究概览
简要总结
Previous studies have clearly demonstrated a significant impact of optimised antibiotic therapy based on a TDM-guided approach in reducing the clinical and microbiological failure rate and in improving the achievement of an optimal pharmacokinetic/pharmacodynamic target. However, no study has yet evaluated this aspect in the specific scenario of liver transplant patients with documented infections with Gram-negative pathogens.
详细描述
Primary aims
- Verify if the attainment of optimal beta-lactam PK/PD targets improves the rate of microbiological eradication in OLT recipients with documented Gram-negative infections;
- Verify if the attainment of optimal beta-lactam PK/PD targets improves the rate of clinical cure in OLT recipients with documented Gram-negative infections.
Secondary aims
- To identify factors independently predicting failure in attaining early optimal beta-lactam PK/PD targets;
- To identify the relationship between the attainment of optimal beta-lactam PK/PD targets and antibiotic resistance development and post-OLT MDR colonization occurrence at 90-days;
- To identify the association between the attainment of optimal PK/PD targets for beta-lactams and variation of inflammatory biomarkers (C-reactive protein [CRP], procalcitonin [PCT], and pro-/anti-inflammatory cytokines, namely IL-6, IL-1, IL-12, IL-8, IL-10, and TNF-α);
- To evaluate the attainment of optimal beta-lactams PK/PD targets at the site of infection in case of pneumonia, intrabdominal and/or biliary infections.
Optimal beta-lactam PK/PD targets will be defined as follows:
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
- •adult OLT recipients (age ≥ 18 years);
- •documented Gram-negative infections occurring in the first 90 days after transplantation;
- •treatment with beta-lactam based-regimens;
- •signed informed consent.
排除标准
- •patients receiving beta-lactam-based regimens for less than 48 hours;
- •patients with isolation of a Gram-negative resistant to all available beta-lactam classes;
- •patients on palliative care and/or not resuscitation order.
结局指标
主要结局
Verify if the attainment of optimal beta-lactam PK/PD targets improves the rate of clinical cure in OLT recipients with documented Gram-negative infections
时间窗: At 30-days from starting antibiotic therapy
Clinical cure, defined as complete resolution of signs and symptoms of the infection coupled with documented microbiological eradication at the end of treatment and the absence of recurrence or relapse at 30-day Dichotomous variable (yes/no)
Verify if the attainment of optimal beta-lactam PK/PD targets improves the rate of microbiological eradication in OLT recipients with documented Gram-negative infections
时间窗: At 30-days from starting antibiotic therapy
Microbiological eradication, defined as the absence of the index pathogen from the primary site of infection in at least two subsequent assessments Dichotomous variable (yes/no)
次要结局
- To identify factors independently predicting failure in attaining early optimal beta-lactam PK/PD targets(At 24 hours after starting antibiotic treatment)
- To identify the relationship between the attainment of optimal beta-lactam PK/PD targets and antibiotic resistance development and post-OLT MDR colonization occurrence at 90-days(At 90-days after starting antibiotic treatment)
- To identify the association between the attainment of optimal PK/PD targets for beta-lactams and variation of inflammatory biomarkers (C-reactive protein [CRP], procalcitonin [PCT], and pro-/anti-inflammatory cytokines(At 7-days after starting antibiotic treatment)
- To evaluate the attainment of optimal beta-lactams PK/PD targets at the site of infection in case of pneumonia, intrabdominal and/or biliary infections(At 7-days after starting antibiotic treatment)