Investigations for Suspected Infective Endocarditis
For patients with suspected infective endocarditis, at least three sets of blood cultures from separate venipuncture sites (drawn at least 1 hour apart) should be obtained before initiating antibiotics, followed by immediate echocardiography to evaluate for vegetations and valvular damage. 1
First-Line Investigations
Microbiological Investigations
- Blood cultures:
- Minimum of 3 sets from separate venipuncture sites
- First and last samples drawn at least 1 hour apart
- Each set should include both aerobic and anaerobic bottles
- Obtain before antibiotic administration
- 10-20 ml of blood per culture bottle to maximize yield 2
Cardiac Imaging
Transthoracic echocardiography (TTE):
Transesophageal echocardiography (TEE):
- Indicated when TTE is negative but clinical suspicion remains high
- Required in most adult patients with suspected IE due to superior sensitivity (76-100%) 3
- Particularly important for prosthetic valves, suspected complications, or poor TTE windows 1
- Essential for detecting paravalvular abscesses and measuring vegetation size 1
Laboratory Tests
- Complete blood count: To assess for leukocytosis and anemia
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): Inflammatory markers
- Renal function tests: To assess kidney function and guide antibiotic dosing
- Urinalysis: To detect hematuria and proteinuria from immune complex deposition
Additional Investigations for Blood Culture-Negative IE
When blood cultures remain negative after 48 hours, additional investigations should be considered 1:
Serological testing for:
- Coxiella burnetii (Q fever) - single positive blood culture or phase I IgG antibody titer >1:800 is a major Duke criterion 1
- Bartonella species
- Brucella species
- Mycoplasma pneumoniae
- Legionella pneumophila
- Aspergillus species
Molecular diagnostic techniques:
- PCR assays for:
- Tropheryma whipplei
- Bartonella species
- Fungi (Candida, Aspergillus)
- PCR assays for:
Autoimmune workup if non-infectious endocarditis is suspected:
- Antinuclear antibodies
- Rheumatoid factor
- Anticardiolipin antibodies (IgG)
- Anti-β2-glycoprotein 1 antibodies (IgG and IgM)
- Anti-pork antibodies (for patients with porcine bioprostheses) 1
Imaging for Complications
Repeat TTE/TEE when:
- New complications are suspected (new murmur, embolism, persistent fever, heart failure)
- Monitoring vegetation size and treatment response
- At completion of antibiotic therapy 1
CT Heart/Chest:
- For evaluating complications like paravalvular abscesses, pseudoaneurysms
- Superior to echocardiography for prosthetic valve assessment
- For detecting septic pulmonary emboli in right-sided endocarditis 1
Diagnostic Algorithm
Initial evaluation:
- Obtain 3 sets of blood cultures
- Perform TTE immediately
If TTE negative but suspicion remains high:
- Proceed to TEE
If blood cultures negative at 48 hours:
- Consult microbiologist
- Consider serological testing panel for atypical organisms
- Consider molecular diagnostic techniques
For prosthetic valve or device-related endocarditis:
- TEE is mandatory
- Consider cardiac CT for better visualization of paravalvular complications
Common Pitfalls to Avoid
- Premature antibiotic administration before adequate blood cultures, leading to culture-negative endocarditis
- Relying solely on TTE when clinical suspicion is high but TTE is negative
- Failure to repeat echocardiography when clinical status changes or complications are suspected
- Overlooking atypical organisms in culture-negative cases
- Not considering non-infectious causes of endocarditis-like presentations
By following this systematic approach to investigations, clinicians can ensure timely diagnosis of infective endocarditis, identify causative organisms, detect complications early, and guide appropriate management to reduce morbidity and mortality.