Infective Endocarditis

Disease Characteristic: Inflammation of the endocardium, typically affecting heart valves

• Types: Acute, subacute, or chronic
• Commonly Affected Valve: Aortic valve (previously mitral valve)
• Common Cause: S. aureus (most fulminant cases)

Causes and Organisms

• Primary Organisms:
  • Staphylococcus aureus (MSSA, MRSA)
  • Coagulase-negative Staphylococci (S. epidermidis, S. lugdenensis)
  • Streptococcus viridans, Streptococcus bovis
  • Enterococcus
  • HACEK organisms (Haemophillus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae)
• Other Causes:
  • Fungi
  • Culture-negative (Brucella, Bartonella, Coxiella burnetti, Chlamydia, Legionella, Mycoplasma, Whipples disease)

Risk Factors

• Cardiac Lesions:
  • Congenital heart disease
  • Rheumatic heart disease
  • Mitral valve prolapse
  • Valve regurgitation
  • Degenerative valve disease
  • Prosthetic valve (early <60 days or late >60 days)
• Predisposition to Infection:
  • IV drug use
  • Hemodialysis
  • High-risk surgeries (dental, respiratory)
  • Long lines
  • Bone marrow transplant recipients
  • Immunosuppression (e.g., HIV)

Pathophysiology

• Normal Endothelium: Resistant to colonization and infection by circulating bacteria.
• Endothelial Damage: Caused by micro-trauma (turbulent flow, intracardiac devices) or chronic diseases (rheumatic heart disease, congenital heart disease, prosthetic valves, previous IE).
• Formation of Sterile Thrombus: Damage produces a fibrin and platelet thrombus which can be seeded by microbes during bacteremia, fungemia, and viremia.

Diagnosis

History

• Focus on preexisting cardiac pathology or clues of bacteremia (IV drug use, intravascular catheters, invasive procedures).
• Non-Specific Symptoms:
  • Fever: 85%
  • Malaise: 80%
  • Weakness, arthralgias, weight loss

Signs

• Atypical Presentation: More likely in elderly, immunocompromised, right heart endocarditis.
• Systemic Signs: Bacteremia/sepsis of unknown cause, fulminant septic and cardiogenic shock.

Clinical Features

• Cardiac Manifestations:
  • New cardiac murmur: 50% of presentations, often regurgitant
  • AV nodal conduction abnormalities: Prolonged PR interval, heart block
  • Heart failure from valvular issues
• Embolic Manifestations:
  • Common initial presentation; incidence of 20-50%
  • Higher risk with S. aureus, Candida, HACEK, Abiotrophia, large or mobile vegetations, mitral valve involvement

Embolic Manifestations

• Renal Emboli: Abscess formation, ischemia, infarction; flank pain, pyuria, hematuria.
• Pulmonary Emboli: Common in IVDU; tricuspid valve involvement; septic emboli, pulmonary infarction, septic pulmonary abscesses.
• Cerebral Emboli: 20% incidence; high mortality rate (40%); second leading cause of death in IE.
• Eye Emboli: Conjunctival and retinal hemorrhages, Roth spots, visual field cuts.
• Splenic Emboli: Flank pain, diaphragmatic irritation, or asymptomatic.

Cutaneous Findings

• Janeway Lesions: Painless hemorrhagic lesions on feet and hands due to septic microemboli.
• Osler Nodes: Tender nodular erythema on fingers, toes, and other areas; likely due to immune complex deposition or microemboli.
• Splinter Hemorrhages: Non-blanchable, reddish-brown to black linear lesions under the nail plate.

Investigations

• Bedside:
  • ECG (look for PR interval widening, dysrhythmia)
• Laboratory:
  • Blood cultures (90% positivity)
  • Serology, rheumatoid factor, PCR for microbial genes
• ECHO:
  • TTE (60% sensitive), TOE (90-99% sensitive)
  • Look for intracardiac masses, abscesses, prosthetic valve issues

Diagnosis

• Modified Duke Criteria:
  • Major Criteria: Positive blood culture, echocardiogram evidence, new valvular regurgitation
  • Minor Criteria: Predisposing heart condition or IV drug use, fever, vascular/immunologic phenomena, microbiological evidence, echocardiographic findings

Management

• Resuscitation
• Specific Therapy: IV antibiotics ± surgery
  • Empiric Treatment:
    • Community-acquired with native valve: Benzylpenicillin + Flucloxacillin + Gentamicin
    • Hospital-acquired/prosthetic valve/penicillin hypersensitivity/CA-MRSA: Vancomycin + Gentamicin
  • Duration: Usually 1-2 weeks (home-based therapy for low-risk patients)
• Surgery Indications: Hemodynamic instability, abscess, recurrent emboli, specific organisms (S. aureus, Q fever, fungal)
• Supportive Care and Monitoring
• Consults: Infectious diseases, cardiology, cardiothoracic surgery

Complications

• Embolic: Major arteries, brain, limbs, lungs, organs
• Sepsis: Local and metastatic abscess formation
• Cardiac: Valve incompetence, heart failure, cardiogenic shock, arrhythmias
• Mortality: Potentially fatal

Prevention

• The approach to prevention is conservative, as the risks of adverse effects from antibiotics can be higher than the risks of developing endocarditis from procedures.
• Antibiotic prophylaxis is recommended for high-risk patients undergoing high-risk procedures.

High-Risk Patients

1. Prosthetic Cardiac Valve or Material: Including bioprosthetic and homograft valves.
2. Previous Infective Endocarditis.
3. Congenital Heart Disease:
   • Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits.
   • Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first six months after the procedure.
   • Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or a prosthetic device.
4. Cardiac Transplant Patients with valve regurgitation due to a structurally abnormal valve.

High-Risk Procedures

1. Dental Procedures: All dental procedures that involve the manipulation of gingival tissue, periapical region of teeth, or perforation of the oral mucosa.
   • Note: Routine anesthetic injections through non-infected tissue, dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, and shedding of deciduous teeth or bleeding from trauma to the lips or oral mucosa do not require prophylaxis.
2. Respiratory Tract Procedures: Involving incision or biopsy of the respiratory mucosa, such as tonsillectomy and adenoidectomy.
3. Surgery: Infected skin, skin structures, or musculoskeletal tissue.

Antibiotic Prophylaxis Regimens

• Timing: Single dose of antibiotic should be given 30-60 minutes before the procedure.

1. Oral Route:
   • Amoxicillin: 2 g orally (children: 50 mg/kg)
2. If Allergic to Penicillin:
   • Cephalexin: 2 g orally (children: 50 mg/kg) – avoid if history of immediate-type hypersensitivity reaction to penicillin.
   • Clindamycin: 600 mg orally (children: 20 mg/kg)
3. Unable to take Oral Medication:
   • Ampicillin: 2 g IM or IV (children: 50 mg/kg)
4. Penicillin-Allergic and Unable to take Oral Medication:
   • Cefazolin or Ceftriaxone: 1 g IM or IV (children: 50 mg/kg)
   • Clindamycin: 600 mg IV (children: 20 mg/kg)

Special Considerations

• Consult Infectious Diseases Specialist: If the patient has a current infection with an organism known to cause endocarditis and requires surgery in the infected area.
• Perioperative Prophylactic Treatment: In cases of surgery on infected areas.

Patient Education

• Educate high-risk patients on the importance of maintaining good oral hygiene and regular dental visits to reduce the risk of bacteremia.
• Advise patients to seek medical advice promptly if they develop signs of infection.

Monitoring and Follow-Up

• Close monitoring for signs of endocarditis after high-risk procedures.
• Follow-up with infectious disease and cardiology specialists as needed.

Feature	Rheumatic Fever (RF)	Infective Endocarditis (IE)
Definition	Inflammatory disease post-group A Streptococcus infection	Infection of the endocardium, typically involving heart valves
Etiology	Autoimmune reaction following group A Streptococcus infection	Direct infection by bacteria or fungi (e.g., Staphylococcus aureus, Streptococcus viridans)
Pathophysiology	Immune response causes inflammation in heart, joints, skin, and brain	Microorganisms enter bloodstream, attach to heart, forming vegetations
Onset	2-4 weeks after streptococcal throat infection	Symptoms can appear rapidly or over weeks/months depending on acute or subacute presentation
Major Clinical Features	Carditis, migratory polyarthritis, Sydenham’s chorea, erythema marginatum, subcutaneous nodules	Fever, new/changing heart murmur, Osler nodes, Janeway lesions, embolic phenomena, Roth spots
	Arthritis: Migratory polyarthritis, which is a hallmark feature. Carditis: Involves all layers of the heart, leading to pancarditis; more likely to cause mitral valve disease. Skin Manifestations: Erythema marginatum (characteristic rash) and subcutaneous nodules. Neurologic Symptoms: Sydenham’s chorea, characterized by involuntary movements and emotional instability. Systemic Symptoms: Malaise and fatigue are less prominent compared to IE.	Fever: Persistent high-grade fever is a prominent feature. Cardiac Symptoms: New or changing heart murmur; heart failure symptoms due to valvular damage. Skin Manifestations: Osler nodes, Janeway lesions, and splinter hemorrhages are more specific to IE. Neurologic Symptoms: Embolic events leading to strokes or other CNS manifestations. Systemic Symptoms: Prominent malaise, fatigue, and weight loss. Embolic Manifestations: Common, affecting various organs (e.g., kidneys, spleen, brain, lungs).
	elevated acute phase reactants ECG: prolonged PR interval	Blood cultures Positive in ~90% of cases; multiple sets needed ECG:May show AV block or conduction abnormalities due to valve involvement
Diagnosis Criteria	Jones Criteria: 2 major or 1 major + 2 minor + evidence of preceding streptococcal infection	Modified Duke Criteria: Positive blood cultures, echocardiographic findings, clinical features
Treatment	Antibiotics (penicillin), anti-inflammatory (aspirin, corticosteroids), long-term penicillin prophylaxis	Prolonged IV antibiotics (vancomycin, gentamicin), possible surgical intervention for valve repair
Complications	Chronic rheumatic heart disease (mitral stenosis), recurrences without prophylaxis	Heart failure, embolic events (stroke, renal infarcts), persistent infection, abscess formation
Prevention	Treat streptococcal infections promptly, long-term antibiotic prophylaxis	Antibiotic prophylaxis for high-risk patients before procedures, good oral hygiene, dental care
Key Clinical Differences	Arthritis, carditis, chorea, subcutaneous nodules, erythema marginatum	Fever, murmur, Osler nodes, Janeway lesions, Roth spots, embolic phenomena
Red Flags	Recent history of streptococcal throat infection. Migratory polyarthritis. Skin rash (erythema marginatum) and subcutaneous nodules. Sydenham’s chorea.	Persistent fever, especially in the presence of a new or changing heart murmur. Positive blood cultures. Signs of embolic events (stroke, renal infarcts, splenic infarcts). Osler nodes, Janeway lesions, and Roth spots.

Key Differences in Clinical Presentation and Red Flags

• Rheumatic Fever:
  • Clinical Presentation: Migratory polyarthritis, carditis, Sydenham’s chorea, erythema marginatum, subcutaneous nodules.
  • Red Flags: Recent history of streptococcal throat infection, migratory arthritis, skin rash (erythema marginatum), chorea.
• Infective Endocarditis:
  • Clinical Presentation: Persistent fever, new or changing heart murmur, Osler nodes, Janeway lesions, Roth spots, embolic phenomena (e.g., stroke, splenic infarcts).
  • Red Flags: Persistent fever, new or changing heart murmur, positive blood cultures, signs of embolic events (e.g., stroke, renal infarcts, splenic infarcts).