Staphylococcus aureus bacteraemia (SAB) is associated with deep focu in 40-50% of cases, through local or haematogenous spread or seeding. Detecting infectious doci in SAB is a prerequisite to source control, which is critical to improving outcomes. However, in 15-20% of cases no focus can be found, and in others additional foci may be missed, which is associated with 50% higher mortality.

Fluoro-2-deoxy-D-glucose (F-FDG) Positron Emission Tomography (PET) is widely used to stage cancer by detecting active cancer cells that metabolise glucose at a higher rate than normal tissues. PET can additionally detect foci of infection, as activated white cells also have high glucose metabolism. PET, when combined with computed tomography (PET/CT), further allows anatomic information to be obtained.

Although previous studies in this area have been small and retrospective, they suggest there may be potential to improve health outcomes. This study aims to improve SAB management using PET/CT through the mechanism of increased detection of foci of infection.

Patients are eligible for this domain if they meet all platform-level inclusion and none of the platform-level exclusion criteria AND all of the domain-level inclusion and none of the domain-level exclusion criteria.

Domain-specific inclusion criteria:

• Patient is at a PET/CT participating site
• Patient is accessible for PET/CT - patients are considered accessible if the site team are able to access the participant's medical records, arrange for a PET/CT scan for the patient, and discuss the domain with the patient and their treating healthcare providers

Domain-specific exclusion criteria:

• Pregnant
• Currently breastfeeding
• <18 years of age
• Patient has had a PET/CT in the past 7 days or needs a PET/CT in the next 7 days
• Clinically unstable for PET/CT
• Contraindication to PET/CT
• Patient no longer willing to participate in the domain
• Clinician deems participation in this domain is not in the patient's best interests

Patients will be randomized to one of the following:

• Usual care with PET/CT

Any decisions on management following PET/CT results will be left to the clinical team and site investigators. Decisions should follow local guidelines, but some further guidance is provided in the Domain-Specific Appendix (not meant to be prescriptive - management decisions that differ are not considered protocol deviations)

• Usual care with no PET/CT

If a patient is randomized to this arm, although PET/CT cannot ethically be forbidden, costs will not be covered by the trial if the treating team deems it necessary for best clinical care

Lead Investigator 1: Dr Anna Goodman

Email: anna.goodman@nhs.net

Lead Investigator 2: Dr Mical Paul

Email: paulm@technion.ac.il

This domain is registered on ClincalTrials.gov: NCT05137119