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INFECTIVE ENDOCARDITIS (IE)

Comprehensive MD Exam Answer — 15 Marks

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DEFINITION

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CLASSIFICATION

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ETIOLOGY / CAUSATIVE ORGANISMS

Native Valve IE:

HACEK Group:

Culture-negative IE Organisms:

• Coxiella burnetii (Q fever), Bartonella spp., Tropheryma whipplei, Brucella spp., fungi (Candida, Aspergillus)

Prosthetic Valve IE (Early <60 days):

• CoNS, S. aureus, gram-negatives, fungi

Prosthetic Valve IE (Late >60 days):

• Viridans streptococci, enterococci (similar to NVE)

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PREDISPOSING CONDITIONS (Risk Factors)

• Rheumatic heart disease (most common in developing countries) — mitral valve most affected
• Congenital heart disease (VSD, PDA, bicuspid aortic valve, TOF)
• Prosthetic valves (mechanical > biological)
• MVP with regurgitation
• Prior IE
• Hypertrophic obstructive cardiomyopathy

• IV drug abuse (IVDA) — tricuspid valve, S. aureus
• Intravascular catheters, pacemakers, ICDs
• Hemodialysis
• Immunosuppression (HIV, malignancy, DM)
• Poor dental hygiene / recent dental procedures
• Elderly patients (degenerative valve disease)

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PATHOGENESIS

Endothelial damage → Platelet-fibrin thrombus (NBTE) → Bacteremia →
Microbial adherence to NBTE → Vegetation formation →
Local destruction + Systemic emboli + Immune complex disease

1. Endothelial injury from turbulent flow, jet lesions, catheters exposes subendothelial matrix
2. Non-bacterial thrombotic endocarditis (NBTE) forms — sterile platelet-fibrin deposits
3. Transient bacteremia (dental, GI, GU procedures or spontaneous) seeds the NBTE
4. Microbial adherence via surface adhesins (fibronectin-binding proteins in S. aureus; dextran in streptococci)
5. Vegetation grows — organisms inside are protected from host defenses and antibiotics (metabolically quiescent, deep within biofilm)
6. Consequences: valve destruction, abscess, emboli, immune complex deposition

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CLINICAL FEATURES

A. Systemic / Constitutional:

• Fever — most common symptom (>90%); may be low-grade or absent in elderly/immunosuppressed
• Chills, night sweats, malaise, anorexia, weight loss
• Arthralgia, myalgia

B. Cardiac Manifestations:

• New/changing murmur — regurgitant murmur (aortic/mitral most common)
• Heart failure — most common cause of death
• Conduction abnormalities — AV block, bundle branch block (suggests perivalvular abscess)
• Pericarditis (rare)

C. Peripheral / Embolic Manifestations:

D. Embolic Complications:

• Stroke (cerebral emboli) — most common CNS manifestation
• Pulmonary emboli (right-sided IE)
• Splenic, renal, mesenteric infarction
• Mycotic aneurysm (cerebral, aortic) — due to seeding of arterial wall

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INVESTIGATIONS

1. Blood Cultures (Cornerstone of Diagnosis)

• 3 sets from different venepuncture sites, before antibiotics
• Drawn ≥1 hour apart (or all 3 within 1 hour in acute/unstable patients)
• Both aerobic and anaerobic bottles; hold for 14 days for fastidious organisms
• Yield: ~90% of cases

2. Echocardiography

• TTE non-diagnostic
• Prosthetic valves
• Staphylococcal bacteremia
• Suspected perivalvular abscess
• Suspected PVE

3. Laboratory Tests:

4. Other Imaging:

• CT scan (brain, chest, abdomen/pelvis): detect emboli, mycotic aneurysms, abscesses
• 18F-FDG PET/CT: useful for PVE, cardiac device IE, occult emboli
• Cardiac MRI: perivalvular extension
• Dental OPG / orthopantomogram: identify dental focus

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DUKE CRITERIA (Modified)

Major Criteria:

1. Positive blood culture for typical organisms:
   • Viridans streptococci, S. gallolyticus, HACEK group, S. aureus, community-acquired enterococci in the absence of a primary focus
   • Persistently positive cultures (>12 h apart, or ≥3 of ≥4 cultures)
   • Single positive culture for Coxiella burnetii OR phase I IgG titer >1:800
2. Evidence of endocardial involvement:
   • Positive echo: oscillating intracardiac mass, abscess, new prosthetic valve dehiscence
   • New valvular regurgitation

Minor Criteria:

1. Predisposing heart condition or IVDA
2. Fever ≥38°C
3. Vascular phenomena: arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, Janeway lesions
4. Immunological phenomena: glomerulonephritis, Osler's nodes, Roth spots, rheumatoid factor
5. Microbiological: positive blood culture not meeting major criteria
6. Echocardiographic: consistent findings not meeting major criteria

Scoring:

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MANAGEMENT

Principles:

• Prolonged bactericidal antibiotics (parenteral) — 4–6 weeks
• Early surgery for high-risk patients
• Multidisciplinary "Endocarditis Team" (cardiologist, cardiac surgeon, infectious disease specialist, microbiologist)

Antibiotic Regimens:

Streptococcal IE (Penicillin-susceptible, MIC ≤0.125 μg/mL):

Staphylococcal IE (MSSA — Native Valve):

• Nafcillin/Oxacillin 12 g/day IV ÷ 6 doses × 6 weeks
• Penicillin-allergic: Cefazolin or Vancomycin

Staphylococcal IE (MRSA or Penicillin-allergic):

• Vancomycin 30–45 mg/kg/day IV ÷ 2–3 doses × 6 weeks
• Or Daptomycin 8–10 mg/kg/day (alternative, cannot use for pulmonary IE)

Enterococcal IE:

• Ampicillin 12 g/day + Gentamicin 3 mg/kg/day × 4–6 weeks
• OR Ampicillin + Ceftriaxone (for high-level aminoglycoside resistance)
• Vancomycin + Gentamicin (if penicillin-allergic)

HACEK organisms:

• Ceftriaxone 2 g/day × 4 weeks
• Or Ampicillin-sulbactam

Prosthetic Valve IE (MRSA):

• Vancomycin + Gentamicin + Rifampicin (600 mg/day, added after 3–5 days) × 6 weeks

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Surgical Indications (Early Surgery):

• Severe AR or MR with heart failure, pulmonary edema, or cardiogenic shock
• Severe AR with hemodynamic compromise
• Fistula into cardiac chamber

• Perivalvular abscess, fistula, false aneurysm
• Enlarging vegetation despite antibiotics
• Fungi or multiresistant organisms
• Persistent bacteremia/fever >7–10 days despite appropriate therapy

• Vegetation >10 mm with prior embolic events
• Very large vegetation (>15 mm)
• Isolated very large vegetation >10 mm with other predictors of complicated course

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COMPLICATIONS

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PROPHYLAXIS

Indications (High-Risk Cardiac Conditions):

1. Prosthetic cardiac valve
2. Previous IE
3. Unrepaired cyanotic CHD
4. Repaired CHD with residual defects near prosthetic material
5. Cardiac transplant with valvulopathy

Procedure:

• Dental procedures involving manipulation of gingival tissue or periapical region of teeth

Regimen:

Note: Prophylaxis is NOT recommended for GI/GU procedures by current AHA/ESC guidelines unless active IE is present.

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PROGNOSIS

• In-hospital mortality: 15–30% overall
• 1-year mortality: up to 40%
• Worse prognosis with: S. aureus, prosthetic valve, perivalvular extension, heart failure, large vegetations, stroke, older age, diabetes
• Better prognosis with: streptococcal IE, early surgery when indicated

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HIGH-YIELD EXAM SUMMARY TABLE

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Sources: Harrison's Principles of Internal Medicine, 21st Edition (p. 3861) | ESC/Management of Endocarditis Guidelines (p. 18) | AHA Endocarditis Guidelines