Top Things to Know: Blood Culture–Negative Endocarditis

Published: March 17, 2025

  1. Infective endocarditis (IE) is an infection of the heart's inner lining, often affecting one or more heart valves. Diagnosis typically relies on positive blood cultures. However, up to 30% of cases—known as blood culture-negative endocarditis (BCNE)—may yield negative results due to recent antibiotic use or infections with difficult-to-culture microorganisms like Coxiella burnetii or Bartonella species.
  2. Advances in imaging and molecular techniques for detecting BCNE pathogens have driven this scientific statement, which addresses the challenges healthcare facilities face and aims to enhance the understanding and management of BCNE.
  3. A comprehensive overview of common clinical scenarios is provided, along with strategies to improve the diagnosis and treatment of BCNE, equipping healthcare professionals with deeper insights.
  4. Non-infectious causes, such as nonbacterial thrombotic endocarditis (NBTE) and rheumatologic conditions, are important considerations in BCNE diagnoses, particularly when infection signs are not prominent, to ensure accurate identification.
  5. Patients with NBTE often present with symptomatic emboli without fever or infection signs, particularly women over 50 with associated malignancies or connective tissue diseases. Stroke, linked to hypercoagulability, is the most common presentation.
  6. A diagnostic approach for BCNE is outlined, including extended blood cultures, serological testing, and considerations for treating Coxiella burnetii, Bartonella, and Brucella. The statement also covers metagenomic sequencing and provides a table of common fastidious BCNE causes with diagnostic and treatment guidance.
  7. Other causes of BCNE are also discussed, such as Bartonellosis, which is transmitted by infected flea feces and is a significant cause of BCNE, often through cat scratches or in individuals experiencing homelessness. The need to consider mycobacterial BCNE, particularly Mycobacterium chimaera from the Mycobacterium avium complex, in patients with delayed-onset prosthetic valve BCNE is highlighted.
  8. Empirical antimicrobial treatments for BCNE are summarized, noting variations in the United States and Europe due to differences in antimicrobial availability, pathogen prevalence, resistance patterns, valve types affected, and presentation timing (e.g., acute vs. subacute).
  9. Timely evaluation by a cardiovascular surgical team is crucial for patients with suspected IE who present with heart failure, severe valve dysfunction, paravalvular abscesses, cardiac fistulas, recurrent embolization, large mobile vegetations, or persistent sepsis despite appropriate antibiotic treatment to determine the optimal timing for surgical intervention.
  10. The challenges of BCNE with unclear echocardiographic findings are addressed, with a discussion on the role of advanced imaging in patients with inconclusive transesophageal echocardiography (TEE) results. Guidance is offered on when to consider cardiac computed tomography, 18F FDG-PET/CT, or WBC SPECT/CT. The statement concludes by outlining future directions and offering prevention tips for the community.

Citation


DeSimone DC, Garrigos ZE, Marx GE, Tattevin P, Hasse B, McCormick DW, Hannan MM, Zuhlke LJ, Radke CS, Baddour LM; on behalf of the American Heart Association Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Clinical Cardiology; and Council on Quality of Care and Outcomes Research. Blood culture–negative endocarditis: a scientific statement from the American Heart Association. J Am Heart Assoc. 2025;14:e040218. DOI: 10.1161/JAHA.124.040218