What are the tests for diagnosing infective endocarditis?

Tests for Diagnosing Infective Endocarditis

The diagnosis of infective endocarditis requires three independent blood culture sets from separate venipuncture sites (with first and last drawn at least 1 hour apart) combined with echocardiography, interpreted using the Modified Duke Criteria. 1

Core Diagnostic Tests

Blood Cultures - The Foundation

• Obtain at least 3 sets of blood cultures from separate venipuncture sites before initiating antibiotics, with the first and last samples drawn at least 1 hour apart 1
• Blood cultures should be incubated under both aerobic and anaerobic conditions 1
• Blood cultures are positive in approximately 90% of IE cases when properly obtained 2
• Critical pitfall: Prior antibiotic administration is the most common cause of blood culture-negative IE (occurring in 2.5-31% of cases), so withdraw antibiotics and repeat cultures if initially negative 1

Echocardiography - Essential Imaging

• Perform transthoracic echocardiography (TTE) first in all suspected cases as the initial imaging modality 1, 2
• Proceed immediately to transesophageal echocardiography (TEE) if:
  • TTE is negative but clinical suspicion remains high 1, 2
  • Prosthetic valve is present 2
  • Intracardiac device leads are present 2
  • Optimal TTE windows cannot be obtained (obesity, COPD, prior cardiac surgery) 1
• TEE has sensitivity of 76-100% for detecting vegetations, compared to only 50-60% for TTE 3
• Repeat echocardiography 7-10 days later if initially negative but clinical suspicion remains high, or earlier if S. aureus infection is suspected 1

Modified Duke Criteria Application

Major Criteria

Blood Culture Criteria 1:

• Typical organisms from 2 separate blood cultures: Viridans streptococci, S. bovis, HACEK group, S. aureus, or community-acquired enterococci
• Persistently positive blood cultures: ≥2 positive cultures drawn ≥12 hours apart, OR all of 3 or majority of ≥4 cultures (with first and last ≥1 hour apart)
• Single positive blood culture for Coxiella burnetii OR phase I IgG antibody titer >1:800

Echocardiographic Criteria 1:

• Vegetation
• Abscess
• New partial dehiscence of prosthetic valve
• New valvular regurgitation

Minor Criteria 1

• Predisposition: predisposing heart condition or injection drug use
• Fever ≥38°C
• Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhages, conjunctival hemorrhages, Janeway lesions
• Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth's spots, rheumatoid factor
• Microbiological evidence: positive blood culture not meeting major criterion OR serological evidence of active infection

Diagnostic Classification 1, 2

Definite IE:

• 2 major criteria, OR
• 1 major + 3 minor criteria, OR
• 5 minor criteria

Possible IE 2:

• 1 major + 1 minor criterion, OR
• 3 minor criteria

Blood Culture-Negative IE: Additional Testing

When blood cultures remain negative at 48 hours and clinical suspicion persists, proceed with specialized testing 1:

Serological Testing 1

Pathogen	Diagnostic Test
Coxiella burnetii	Serology (IgG phase I >1:800)
Bartonella spp.	Serology + blood cultures
Brucella spp.	Blood cultures + serology
Mycoplasma spp.	Serology
Legionella spp.	Blood cultures + serology

Molecular Diagnostics

• PCR testing on blood samples or surgical specimens for Tropheryma whipplei, Bartonella spp., and fungi (Candida spp., Aspergillus spp.) 1, 4
• 16S rRNA gene PCR/sequencing on resected valve tissue 4, 5
• Metagenomic next-generation sequencing shows promising results for culture-negative cases 6

Histopathological Examination

• Pathological examination of resected valvular tissue or embolic fragments remains the gold standard for diagnosis 1
• All surgical specimens should be collected in sterile containers without fixative and sent immediately to microbiology 1
• Perform Gram stain, culture, immunohistology, and cryopreservation for possible PCR 1

Non-Infectious Causes to Consider

When all microbiological assays are negative, test for 1:

• Antinuclear antibodies
• Antiphospholipid syndrome (anticardiolipin antibodies IgG, anti-β2-glycoprotein 1 antibodies IgG and IgM)
• Anti-pork antibodies (if patient has porcine bioprosthesis with allergic markers)

Critical Management Points

• Early consultation with infectious disease specialist is recommended, especially for culture-negative cases or atypical organisms 1
• Refer complicated cases to reference centers with multidisciplinary "Endocarditis Teams" including cardiologist, infectious disease specialist, cardiac surgeon, and microbiologist 7, 2
• Repeat blood cultures 48-72 hours after starting treatment to verify effectiveness 1
• The Duke criteria are meant to guide diagnosis but must not replace clinical judgment - clinicians may appropriately decide to treat regardless of whether criteria are met 1