Prospective, Randomized Controlled Trial to Evaluate the Impact of a Procalcitonin Testing and Treatment Algorithm on Antibiotic Use and Outcomes in the Pediatric Intensive Care Unit
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 271
- 试验地点
- 2
- 主要终点
- Days of Antibiotic Therapy in the First 14 Days Following Randomization
研究概览
简要总结
The timely use of antibiotics can reduce morbidity and mortality associated with bacterial infections, particularly in the intensive care unit setting (ICU). Long courses of antibiotics, however, are associated with the emergence of multi-drug resistant organisms and antibiotic-associated adverse events, such as C. difficile infections. Thus, antibiotic de-escalation is an important goal of antimicrobial stewardship programs.
Procalcitonin (PCT) has been investigated as a biomarker for critically ill adult patients with bacterial infection, particularly pneumonia and sepsis. The proposed project will evaluate whether a PCT testing and treatment algorithm, implemented through daily antimicrobial stewardship audit and feedback, can promote early and safe antibiotic de-escalation in the pediatric ICU.
详细描述
The timely use of effective antibiotics can markedly reduce the morbidity and mortality associated with bacterial infections, particularly in the intensive care unit (ICU). However, in this setting, much antibiotic use is empiric, and administered to patients with non-bacterial or non-infectious causes of inflammation that do not respond to antibiotics. This widespread empiric use of antibiotics drives the emergence of multi-drug resistant organisms and antibiotic-associated adverse events, such as C. difficile infections. De-escalation of broad-spectrum empiric antibiotics for ICU patients without proven bacterial infections can reduce unnecessary antibiotic use, slow the development of antibiotic resistance, and reduce complications associated with antibiotic therapy. Thus, antibiotic de-escalation is an important goal of antimicrobial stewardship programs. Specific tests and pathways to predict which patients have bacterial infections and those that would benefit from antibiotic therapy would accelerate de-escalation and greatly facilitate antimicrobial stewardship efforts.
Procalcitonin (PCT) has been investigated as a biomarker for critically ill adult patients with bacterial infection, particularly pneumonia and sepsis. Following bacteria-induced activation of monocytes and adherence of monocytes to endothelial surfaces, procalcitonin is expressed and secreted. PCT levels have been shown to rise rapidly and remain elevated during ongoing bacterial infections, and PCT levels are more specific for bacterial infections than CRP or total white blood cell count. PCT rises approximately 4 hours after bacterial exposure, peaks between 12-24 hours, and has a half-life of 24 hours once the infectious stimulus is removed.
In many adult trials investigating PCT-guided algorithms for antibiotic cessation (refer to section 3.0), a high proportion of providers (up to 50%) chose not to follow algorithm guidance for subjects randomized to the PCT-guided group. Thus, although PCT appears to be a useful guide for safe antibiotic de-escalation in the ICU, the ideal method for implementing the test and integrating it into clinical care in order to maximize its impact in the pediatric population is unclear. Notably, none of the prior trials evaluated PCT-associated outcomes in critically ill children nor integrated PCT testing into antimicrobial stewardship activities.
The investigators propose the evaluation of a PCT testing and treatment algorithm on patient outcomes in the pediatric ICU, a setting in which PCT-guided antibiotic de-escalation has not been previously studied.
The proposed project will evaluate whether a procalcitonin (PCT) testing and treatment algorithm, implemented through daily antimicrobial stewardship audit and feedback, can promote early and safe antibiotic de-escalation in the pediatric ICU. The investigators will conduct a pragmatic, prospective randomized controlled trial comparing antimicrobial use and outcomes among children admitted to the ICU who receive either: 1) Routine laboratory testing and treatment with antimicrobial stewardship review (control), or 2) PCT testing and treatment with antimicrobial stewardship review (intervention). In both arms, baseline daily review of antimicrobial management by the stewardship team will occur. In the intervention arm, the stewardship provider also will recommend PCT testing and antibiotic modifications using a PCT-based treatment algorithm. PCT levels will be measured a total of four times in the intervention arm - on enrollment, then daily through day 3 post-randomization and on day 5 post-randomization. This research is not to determine if PCT is a good test; this has already been established and evaluated as part of the FDA approval process. This pragmatic outcomes trial is evaluating if use of the PCT, implemented together with antimicrobial stewardship program oversight, improves the quality of care the investigators can provide for children at Vanderbilt Children's Hospital. The investigators hypothesize that patients in the intervention arm will have shorter duration of antibiotic therapy and similar outcomes, as compared to patients in the control arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Hours 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years of age or younger
- •Prescribed or administered antibiotics in the hospital less than or equal to 24 hours prior to enrollment
- •Have parents or legal guardians who provide informed consent
- •Provide assent (if > 7 years of age)
排除标准
- •Are not prescribed antibiotics in the hospital
- •Receive intravenous antibiotics within 7 days prior to identification for study enrollment
- •Primary or secondary immune deficiency
- •History of malignancy, bone marrow transplant or solid organ transplant
- •A diagnosis of cystic fibrosis
- •Neonates < 34 weeks gestation
- •Patients receiving treatment for endocarditis, osteomyelitis, meningitis, mediastinitis or other invasive infection, for which long duration of antibiotics is needed
- •Do not provide informed consent/assent
结局指标
主要结局
Days of Antibiotic Therapy in the First 14 Days Following Randomization
时间窗: 14 days
Days of antibiotic therapy a participant receives following randomization will be measured
次要结局
- Re-initiation of Antibiotics for a Bacterial Infection(up to 30 days)
- Number of Participants With Antibiotic-associated Complications(up to 14 days)
- Antibiotic Cost(up to 14 days)
- Duration of Broad-spectrum Antibiotic Therapy(up to14 days)
- Number of Patients With an Antibiotic Change(up to 14 days)
- 30-day Mortality(up to 30 days)
- Length of Intensive Care Unit Stay(up to 14 days)
- Ventilator Days(up to 14 days)
- Infection With a Multi-drug Resistant Organism(up to 30 days)
- Length of Overall Hospital Stay(Until hospital discharge, an average of 7 days)
- Number of Participants Whose Provider Adhered to the Procalcitonin-guided Algorithm(up to 5 days)
研究者
Sophie Katz
Postdoctoral Fellow
Vanderbilt University Medical Center