Recommended Tests for Diagnosing Infective Endocarditis
Blood cultures and echocardiography are the cornerstones of infective endocarditis diagnosis, with three sets of blood cultures from separate venipuncture sites required before initiating antibiotics, followed by transthoracic echocardiography and, if needed, transesophageal echocardiography. 1, 2
Blood Culture Collection
- Obtain three sets of blood cultures from separate venipuncture sites
- First and last samples should be drawn at least 30 minutes apart
- Each set should include aerobic and anaerobic bottles
- Collect at least 10 ml of blood per bottle for adults
- Perform BEFORE initiating antimicrobial therapy
- If initial cultures are negative after 48 hours, obtain additional sets
Echocardiography
- Transthoracic echocardiography (TTE) as first-line imaging (sensitivity 50-60%)
- Transesophageal echocardiography (TOE/TEE) if TTE is negative but suspicion remains high (sensitivity 76-100%)
- TEE is particularly valuable for:
- Prosthetic valve endocarditis
- Suspected paravalvular complications
- Small vegetations
- Cardiac device-related IE
Modified Duke Criteria
Diagnosis is based on the Modified Duke Criteria, which include:
Major Criteria
Positive blood cultures:
- Typical microorganisms from two separate blood cultures
- Persistently positive blood cultures (≥2 samples drawn >12h apart or majority of ≥4 cultures)
- Single positive blood culture for Coxiella burnetii or phase I IgG antibody titer >1:800
Evidence of endocardial involvement:
- Positive echocardiogram showing vegetation, abscess, new partial dehiscence of prosthetic valve, or new valvular regurgitation
- Abnormal activity around prosthetic valve detected by 18F-FDG PET/CT (if prosthesis >3 months old) or radiolabelled leukocyte SPECT/CT
Minor Criteria
- Predisposing heart condition or injection drug use
- Fever (≥38°C)
- Vascular phenomena (emboli, septic infarcts, mycotic aneurysm, etc.)
- Immunologic phenomena (glomerulonephritis, Osler's nodes, etc.)
- Microbiological evidence not meeting major criteria
Tests for Culture-Negative Endocarditis
When blood cultures remain negative after 48 hours, additional tests should include:
Serological Testing
- Coxiella burnetii (Q fever)
- Bartonella species
- Brucella species
- Legionella pneumophila
- Mycoplasma pneumonia
- Aspergillus species
Molecular Diagnostic Techniques
- PCR from blood or excised valve tissue for:
- Tropheryma whipplei
- Bartonella species
- Fungi (Candida, Aspergillus)
- Broad-range 16S and 18S rRNA PCR
Immunological Testing
- Rheumatoid factor
- Antinuclear antibodies
- Antiphospholipid antibodies
- Anti-pork antibodies (for patients with porcine bioprosthesis)
Advanced Imaging for Complicated Cases
- Cardiac CT: Useful for evaluating paravalvular complications
- 18F-FDG PET/CT: Valuable for prosthetic valve endocarditis diagnosis
- Radiolabelled leukocyte SPECT/CT: Considered a major criterion in the 2015 ESC guidelines
Monitoring During Treatment
- Repeat blood cultures every 24-48 hours until negative
- Inflammatory markers (CRP, ESR, procalcitonin)
- Complete blood count with differential
- Renal function tests (BUN, creatinine)
- Cardiac biomarkers (troponins, CK)
- Follow-up echocardiography to monitor vegetation size and complications
Common Pitfalls to Avoid
- Initiating antibiotics before obtaining blood cultures, which significantly reduces diagnostic yield
- Relying solely on TTE when suspicion is high (TEE has much higher sensitivity)
- Overlooking culture-negative endocarditis when standard cultures are negative
- Failing to consider non-infectious causes of endocarditis-like presentations
- Not repeating blood cultures to document clearance of bacteremia
The diagnosis of IE requires a systematic approach using these diagnostic tests, with interpretation guided by the modified Duke criteria. Early consultation with infectious disease specialists and cardiologists is recommended for optimal management.