What are the diagnostic criteria and treatment options for infective endocarditis?

Infective Endocarditis Diagnostic Criteria

The diagnosis of infective endocarditis is based on the Modified Duke Criteria, which classify cases as definite, possible, or rejected using a combination of major criteria (blood cultures and imaging findings) and minor criteria (clinical and laboratory features). 1

Diagnostic Categories

Definite IE is diagnosed when any of the following are met 1, 2:

• Pathological criteria: Microorganisms demonstrated by culture or histology from vegetation, embolized vegetation, or intracardiac abscess specimen
• Clinical criteria:
  • 2 major criteria, OR
  • 1 major criterion + 3 minor criteria, OR
  • 5 minor criteria

Possible IE is diagnosed with 1, 2:

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

Rejected IE applies when 1, 2:

• Firm alternative diagnosis explains the clinical findings
• Resolution of syndrome with ≤4 days of antibiotic therapy
• No pathological evidence at surgery/autopsy after ≤4 days of antibiotics
• Does not meet criteria for possible IE

Major Criteria

Blood Culture Criteria

Typical microorganisms from ≥2 separate blood cultures 1, 2:

• Viridans streptococci
• Streptococcus gallolyticus (S. bovis)
• HACEK group organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)
• Any Staphylococcus aureus bacteremia (community-acquired or nosocomial, regardless of removable source) 2, 3
• Community-acquired enterococci in absence of primary focus

Persistently positive blood cultures 1, 2:

• ≥2 positive cultures drawn >12 hours apart, OR
• All of 3 or majority of ≥4 separate cultures (first and last ≥1 hour apart)

Single positive blood culture for Coxiella burnetii OR anti-phase I IgG antibody titer >1:800 1, 2

Imaging Criteria

Echocardiogram positive for IE 1, 2:

• Oscillating intracardiac mass on valve or supporting structures, in path of regurgitant jets, or on implanted material
• Abscess, pseudoaneurysm, intracardiac fistula
• Valvular perforation or aneurysm
• New partial dehiscence of prosthetic valve
• New valvular regurgitation (worsening of pre-existing murmur is NOT sufficient) 1, 2

Advanced imaging for prosthetic valves (>3 months post-implantation) 1:

• Abnormal activity around prosthetic valve on ¹⁸F-FDG PET/CT
• Abnormal activity on radiolabeled leukocyte SPECT/CT

Minor Criteria

Predisposing conditions 1, 2:

• Predisposing heart condition (mitral valve prolapse, bicuspid aortic valve, valve stenosis/regurgitation, prior IE)
• Injection drug use

Fever ≥38.0°C 1, 2

Vascular phenomena (including imaging-detected silent events) 1, 2:

• Major arterial emboli
• Septic pulmonary infarcts
• Mycotic aneurysm
• Intracranial hemorrhage
• Conjunctival hemorrhages
• Janeway lesions

Immunologic phenomena 1, 2:

• Glomerulonephritis
• Osler's nodes
• Roth's spots
• Positive rheumatoid factor

Microbiological evidence not meeting major criterion 1, 2:

• Positive blood culture not meeting major criterion
• Serological evidence of active infection with organism consistent with IE

Diagnostic Algorithm

Step 1: Clinical suspicion - Consider IE in patients with 1:

• Unexplained fever >72 hours + pathological murmur or prosthetic valve
• Fever + predisposing cardiac condition
• S. aureus bacteremia from any source

Step 2: Obtain blood cultures BEFORE antibiotics 2:

• Draw ≥3 blood culture sets from separate venipunctures
• Critical pitfall: Premature antibiotic administration is the leading cause of culture-negative endocarditis 2
• For non-acutely ill patients with negative cultures, withhold antibiotics ≥48 hours to improve diagnostic yield 4

Step 3: Echocardiography 1:

• Start with transthoracic echocardiography (TTE)
• Proceed to transesophageal echocardiography (TEE) if:
  • TTE is technically inadequate, nondiagnostic, or negative
  • Prosthetic valve present
  • High clinical suspicion despite negative TTE
• TEE detects vegetations in >95% of cases vs. 60-75% for TTE 1

Step 4: Advanced imaging when TTE/TEE equivocal 1:

• Cerebral MRI for embolic events
• Whole body CT for extracardiac complications
• ¹⁸F-FDG PET/CT or radiolabeled leukocyte SPECT/CT for prosthetic valve IE

Critical Pitfalls to Avoid

Do not dismiss S. aureus bacteremia - Any S. aureus bacteremia should be considered a major criterion regardless of whether it appears nosocomial or has an apparent removable source 2, 3. This organism causes IE in 80% of tricuspid valve infections and is frequently missed when attributed to other sources 1.

Culture-negative endocarditis occurs in 63-71% of cases, primarily due to prior antibiotic use 5. When cultures remain negative, consult infectious disease specialists for molecular pathogen identification and serological testing (especially Q-fever serology) 4.

The Modified Duke Criteria have 80% sensitivity in pathologically proven cases 2, 6, meaning 20-24% of true IE cases may be misclassified as "possible" 7. When clinical suspicion remains high despite "possible" classification, do not reject the diagnosis - proceed with treatment and repeat imaging 1.

Echocardiography and blood cultures remain the cornerstone of diagnosis 1. The criteria do not replace clinical judgment by an experienced Endocarditis Team, particularly in complex cases with negative cultures or equivocal imaging 1.

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