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Background Blood culture negative infective endocarditis (BCNIE) is often a diagnostic challenge in adult congenital heart disease patients leading to misdiagnosis, treatment delay and associated high mortality. Studies of BCNIE in adult congenital heart disease patients repaired with prosthetic cardiovascular grafts are limited. Case summary We report two cases of BCNIE where serology testing, multiple polymerase chain reaction testing of explanted valve material and multi-modality imaging including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were utilized not only to confirm the diagnosis but also to guide management strategy and inform prognosis. Both patients were treated successfully with cardiac surgery and prolonged anti-microbial therapy. Discussion Clinical presentation of BCNIE in repaired CHD patients is highly variable. The symptoms are often non-specific with subacute or chronic presentation. This may mislead initial diagnosis and subsequent management. Multi-modality imaging including PET/CT should be considered to support the diagnosis, define the extent of infection, decide the management strategy and inform prognosis in patients. A thorough history of animal exposure, and consideration of serology and multiple molecular testing to identify the causative organism, is critical in the management of BCNIE.

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