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Infective Endocarditis (IE) - Complete Teaching Guide

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What is Infective Endocarditis?

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1. Acute vs. Subacute IE

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2. Common Organisms - "WHO causes IE?"

A) Viridans Streptococci (e.g., S. sanguis, S. mutans)

• Origin: Normal oral flora (mouth/teeth)
• Entry: Dental procedures, poor oral hygiene
• Type: Subacute IE - attacks damaged or deformed valves (rheumatic heart disease, MVP)
• Virulence: Low - it's slow and sneaky
• Quick memory: "Viridans = Valve already damaged + Very slow"
• Historically the most common cause (50-60% of community IE); remains important in developing countries

B) Staphylococcus aureus

• Origin: Skin flora
• Entry: IV drug use, healthcare procedures (catheters, surgery), skin breaks
• Type: Acute IE - attacks healthy AND damaged valves
• Special: Now the #1 cause in developed countries and in IV drug users (attacks the tricuspid valve in IVDU)
• Virulence: High - produces toxins, biofilm, destroys valve rapidly
• Quick memory: "Staph = Speedy Skin bug; goes for Surgical sites + Shooting up"

C) HACEK Group

• H - Haemophilus species
• A - Aggregatibacter species (formerly Actinobacillus)
• C - Cardiobacterium hominis
• E - Eikenella corrodens
• K - Kingella kingae
• Origin: Normal oral cavity and upper respiratory commensals
• Type: Subacute IE
• Key feature: Slow-growing, fastidious gram-negative rods - hard to culture, need prolonged incubation (up to 3 weeks)
• Quick memory: "HACEK bugs HACK their way in from the mouth, grow SLOWLY in the lab"

Other Organisms to Know:

~10% of all IE cases are culture-negative - due to prior antibiotics or fastidious organisms (Q fever/Coxiella burnetii, Bartonella, Brucella, T. whipplei).

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3. Blood Culture Method - "How to Catch the Bug"

Rules of Blood Culture in IE:

1. 3 sets of blood cultures - take them from 3 separate venipuncture sites
2. Each set = 1 aerobic + 1 anaerobic bottle
3. Timing: Ideally spread over at least 1 hour (or up to 24 hours if subacute + stable)
4. Do NOT delay antibiotics if patient is septic or hemodynamically unstable - take 3 sets quickly then treat
5. If stable and subacute: Withhold antibiotics for up to 2 weeks to maximize culture yield
6. Volume matters: 10 mL per bottle is ideal

Why 3 separate sites?

• IE produces continuous bacteremia (not intermittent like with abscesses)
• So ANY culture should be positive - getting multiple sets helps confirm true bacteremia vs. contaminant
• Sensitivity: 95-99% with 3 sets if no prior antibiotics

Special cultures for hard-to-grow organisms:

• HACEK: Need prolonged incubation (14-21 days), tell the lab!
• Q fever (Coxiella): Serology (IgG phase 1 antibody ≥1:800)
• Bartonella: Serology or PCR
• Culture-negative IE: Use broad-range 16S rRNA PCR on blood or excised valve tissue

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4. Duke's Criteria - "How to Diagnose IE"

MAJOR Criteria (think: "Big Ticket Items")

1. Typical organism in 2 separate blood cultures:
   • Viridans streptococci, S. bovis, HACEK group, S. aureus, OR enterococcus (community-acquired, no primary focus)
2. Persistently positive blood cultures (same organism):
   • ≥2 positive cultures drawn >12 hours apart, OR
   • All of 3 or majority of ≥4 separate cultures with first and last drawn ≥1 hour apart
3. Single positive blood culture for Coxiella burnetii OR IgG antibody titer >1:800

• Vegetation (oscillating intracardiac mass on valve)
• Valvular perforation or aneurysm
• Abscess or pseudoaneurysm
• Intracardiac fistula
• New significant valvular regurgitation (new, compared to prior imaging)
• New partial dehiscence of prosthetic valve
• 18F-FDG PET/CT: Abnormal metabolic activity around native/prosthetic valve (≥3 months post-implant)

• Direct visualization of IE at cardiac surgery (when micro/imaging criteria not met)

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MINOR Criteria (think: "Supporting Evidence")

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How to Apply Duke Criteria

• 2 Major = DEFINITE (like 2 big witnesses confirming the crime)
• 1 Major + 3 Minor = DEFINITE (1 solid + 3 supporting)
• 5 Minor = DEFINITE (5 circumstantial = enough to convict)

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5. Peripheral Stigmata - "The Classic Signs"

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6. Echocardiography

• TTE (Transthoracic Echo): First-line; specific but misses 20-35% of vegetations
• TEE (Transesophageal Echo): >90% sensitivity for vegetations; use when:
  • TTE is negative but suspicion is high
  • Prosthetic valve involved
  • S. aureus bacteremia
  • Poor TTE image quality
  • Looking for abscesses, perivalvular complications
• Repeat TEE in 7-10 days if initial is negative but IE still suspected

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7. Treatment - "How to Kill the Bug"

Principles:

1. Bactericidal antibiotics required (not just bacteriostatic) - vegetation is avascular
2. Prolonged therapy - 4-6 weeks (to penetrate biofilm and kill embedded organisms)
3. IV route preferred (high concentrations needed)
4. Guided by organism and susceptibility

Treatment by Organism:

• Preferred: Penicillin G IV × 4 weeks, OR Ceftriaxone 2g IV/IM once daily × 4 weeks
• Shorter option: Penicillin G or Ceftriaxone × 2 weeks + Gentamicin × 2 weeks (native valve only, uncomplicated)
• Penicillin allergy: Vancomycin × 4 weeks

• MSSA (Methicillin-Sensitive):
  • Native valve: Nafcillin or Oxacillin IV × 6 weeks
  • Prosthetic valve: Nafcillin + Rifampin × ≥6 weeks + Gentamicin × 2 weeks
• MRSA:
  • Vancomycin IV × 6 weeks OR Daptomycin (high-dose, ≥8 mg/kg/day) × 6 weeks
  • Note: Daptomycin NOT used for pulmonary IE (inactivated by surfactant)
• Tricuspid valve IE (IVDU): Often treated with short-course (2 weeks) oral therapy if uncomplicated and MSSA

• Preferred: Ceftriaxone 2g/day IV × 4 weeks (most HACEK produce beta-lactamase)
• Alternative: Ampicillin-sulbactam OR ciprofloxacin (if susceptible)

• Ampicillin + Ceftriaxone × 6 weeks (E. faecalis, less nephrotoxic than aminoglycoside regimens)
• OR Penicillin/Ampicillin + Gentamicin × 4-6 weeks (synergy required)
• VRE (E. faecium): High-dose daptomycin-based regimen

• Native valve: Ampicillin-sulbactam or Vancomycin ± Gentamicin
• Prosthetic valve: Vancomycin + Gentamicin + Rifampin

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Indications for Surgery (when antibiotics alone are NOT enough):

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8. Complications - "What can go wrong?"

1. Cardiac: Heart failure (most common cause of death), perivalvular abscess, conduction defects (AV block - extension to septum), pericarditis
2. Embolic: Stroke, splenic/renal infarcts, mycotic aneurysms, septic pulmonary emboli (right-sided IE)
3. Renal: Immune complex glomerulonephritis, renal infarction, drug nephrotoxicity
4. Other: Splenic abscess (3-5%), metastatic abscesses

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9. Prophylaxis

• Prosthetic cardiac valve or repair material
• Prior IE
• Unrepaired cyanotic congenital heart disease
• Cardiac transplant with valvulopathy
• Ventricular assist devices and implantable hearts (NEW in 2021)

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Summary Flowchart in Words

Fever + Risk Factor (IVDU, dental work, prosthetic valve)
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Draw 3 blood cultures from separate sites
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Echo (TTE → TEE if TTE negative/inadequate)
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Apply Duke Criteria
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Start targeted antibiotic therapy (4-6 weeks IV)
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Monitor for complications (HF, embolism, abscess)
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Surgery if indicated

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Quick Revision Table - "The Big Picture"

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• IE organisms in more clinical detail
• Blood culture techniques and lab methods
• Bacterial identification (HACEK, Streptococci, Staph)
• Antibiotic sensitivity patterns