Accuracy of Metagenomic Blood Sampling to Identify Pathogen in Infective Endocarditis Patients

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%.

The Quadram Institute (QI) is a Biotechnology and Biological Sciences Research Council (BBSRC) funded research institute has special expertise in CMg, including two Nature papers.

This study of 200 patients will assess the accuracy of blood CMg and identify the best time to sample along with its cost effectiveness. Patients will be asked for an extra 10 mL of blood which will be sent to QI along with a routinely taken admission blood sample.

In addition if surgery is clinically required, some of the resected heart valve tissue will also be sent for CMg analysis Results from CMg will be compared to blood culture. A control group of patients undergoing valve surgery for non-IE indications will also be recruited.

To assist future commissioning of a clinical CMg service within the NHS, a cost-effectiveness analysis of use of CMg in the endocarditis diagnosis and treatment pathway will be developed.

Inclusion criteria

• Patients with possible or confirmed IE referred to BHC Endocarditis MDT
• Age >18
• Able and willing to give informed consent

Exclusion criteria

• 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.