Accuracy of Metagenomic Blood Sampling to Identify Pathogen in Infective Endocarditis Patients
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Diagnostic accuracy of CMg in blood
研究概览
简要总结
Infective Endocarditis is an infection, usually a bacterium, which attacks the heart and can cause valves to leak and produces a bacterial mass which can break off from the valves and block the blood supply to important organs.
We are very keen to improve the treatment of this disease and we are measuring the impact of the treatments that we give to patients so that we have a very clear idea of which treatments work best and also which treatments are less successful.
A key part of the treatment is the accurate determination of the causative organism which allows appropriate targeted antibiotic and antifungal medication to be administered.
Accurate antibiotic regimes require detection of the causative organism and its sensitivities to each antibiotic. Antibiotic choice is then based on effectiveness, toxicity, ease of use and national guidelines. The current best technique for identifying bacteria is blood culture where organisms are identified by growing them from blood samples. However, this takes up to 5 days from sampling, resulting in delays to the correct diagnosis. Until this time, treatment requires the use of generic, more toxic antibiotic regimes.
New techniques are emerging to identify causative organisms from blood. Metagenomics allows the sequencing of bacterial DNA allowing precise identification of the infecting organism.
详细描述
Infective Endocarditis (IE) occurs when bacteria or fungi settle on heart valves and damage the tissues. The disease can be catastrophic and result in death, heart failure, stroke, kidney failure and other complications. Valvular damage requires cardiac surgery in approximately 50% with endocarditis; early antibiotic treatment reduces complications and improves prognosis, reducing the need for surgery. This is dependent on rapid, accurate determination of the causative organism to administer effective and targeted antimicrobial therapy.
The current best technique for identifying bacteria is blood culture - organisms are identified by growing them from blood. However, this typically takes up to 5 days.
In up to 18% of patients, blood culture fails to identify a causative organism - Blood Culture Negative Infective Endocarditis (BCNIE). As a result, patients are treated with broader spectrum antibiotics which have greater toxicity than targeted regimens, resulting in higher complication rates. Alternative technologies to standard blood culture are therefore needed.
Clinical metagenomics (CMg) allows the sequencing of bacterial DNA from blood samples allowing precise, rapid identification of the pathogen. Hitherto, this technology was expensive and limited. New technology is changing the face of CMg and will potentially allow organisms to be rapidly identified at low cost.
Barts Heart Centre (BHC) is one of the largest cardiac centres in the world, managing 150 IE cases annually. Whilst mortality for IE remains high - 17.1% in the recently published EuroENDO study - in hospital mortality at Barts Heart Centre is ~13%.
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
- 是
入选标准
- •Patients with possible or confirmed IE referred to BHC Endocarditis MDT
- •Able and willing to give informed consent
排除标准
- •Patients whose diagnosis of endocarditis is "rejected" by the MDT. If this occurs after entry to the study samples will be discarded and the patient informed.
- •Patients who have been treated with intravenous antibiotics for more than 7 days at the time of study entry.
结局指标
主要结局
Diagnostic accuracy of CMg in blood
时间窗: 3 years
The primary objective of this study is to compare the organisms found from metagenomic testing of blood samples with organisms found from blood culture from a prospective series of sequential patients with IE and compared to blood culture, surgically-resected valve tissue culture (where surgery is undertaken) and opinion of a clinical reference group
次要结局
- To evaluate the results of Nanopore CMg in identifying the causative organism in patients with BCNIE(3 years)
- 1. Optimal timing of blood sampling(3 years)
- 3. Metagenomic Techniques(3 years)