Agents of Endocarditis

Endocarditis, the inflammation of the heart’s inner lining (endocardium), including the valves, is a serious and life-threatening infection. Bacteremia is a major risk factor. The rapid and accurate identification of the causative agents is crucial for guiding appropriate antimicrobial therapy and improving patient outcomes

Common Agents of Endocarditis

Staphylococcus aureus

• Prevalence: The most common cause of endocarditis, particularly in intravenous drug users (IVDUs), patients with prosthetic valves, and healthcare-associated infections
• Characteristics: Often rapidly progressive, with severe valvular damage
• Virulence: Highly virulent, producing toxins and enzymes that contribute to tissue damage and spread
• Clinical Presentation: Fever, chills, new heart murmur, embolic events (e.g., stroke, pulmonary emboli), skin manifestations (e.g., petechiae, Osler’s nodes, Janeway lesions)
• Treatment: Requires aggressive antibiotic therapy, often combined with surgical intervention (e.g., valve replacement)

Coagulase-Negative Staphylococci (CoNS)

• Prevalence: Common cause, especially for prosthetic valve endocarditis, but also in native valve infections
• Characteristics: Often associated with indwelling devices (e.g., central venous catheters, pacemakers)
• Species: Most commonly, Staphylococcus epidermidis
• Clinical Presentation: Often a more indolent course than S. aureus, with fever, new heart murmur, and potentially embolic events
• Antibiotic Resistance: CoNS often exhibit antimicrobial resistance, especially to beta-lactam antibiotics, making treatment challenging

Streptococcus spp.

• Prevalence: Streptococcus species are a significant cause of endocarditis
• Types
  • Streptococcus viridans group: The most common Streptococcus species causing endocarditis. These are normal inhabitants of the oral cavity and upper respiratory tract
  • Streptococcus bovis group: Associated with colon cancer and other gastrointestinal disorders
  • Other Streptococci: including Streptococcus pneumoniae and Streptococcus pyogenes, are less common but can cause endocarditis
• Characteristics: Can cause both acute and subacute endocarditis. May be associated with dental procedures or other invasive procedures
• Clinical Presentation: Fever, new heart murmur, embolic events. Can cause a more gradual onset of symptoms than S. aureus
• Treatment: Typically responds well to penicillin-based antibiotics

Enterococcus spp.

• Prevalence: Important cause, especially in healthcare-associated endocarditis and IVDU
• Characteristics: Can cause both native and prosthetic valve endocarditis. Often associated with urinary tract infections (UTIs) and gastrointestinal infections
• Species: Primarily Enterococcus faecalis and Enterococcus faecium
• Antibiotic Resistance: Enterococcus species are often resistant to multiple antibiotics, including vancomycin (VRE), posing significant treatment challenges
• Clinical Presentation: Fever, new heart murmur, embolic events. Can cause a more indolent course
• Treatment: Requires combination antibiotic therapy, sometimes including agents like ampicillin, vancomycin, and aminoglycosides

Gram-Negative Bacteria

• Prevalence: Less common than gram-positive organisms, but are important causes of endocarditis
• Characteristics: Often associated with healthcare-associated infections, IVDU, and prosthetic valve infections
• Types
  • HACEK organisms: A group of fastidious gram-negative bacteria: Haemophilus spp., Aggregatibacter spp. (formerly Actinobacillus), Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae
  • Pseudomonas aeruginosa: A pathogen in IVDU and prosthetic valve endocarditis. Often difficult to treat due to antibiotic resistance
  • Enterobacteriaceae (e.g., Escherichia coli, Klebsiella pneumoniae): Can cause endocarditis, particularly in patients with indwelling devices or other risk factors
  • Clinical Presentation: Fever, new heart murmur, embolic events. Can cause a more acute or chronic course, depending on the organism
• Treatment: Antibiotic therapy typically includes broad-spectrum agents, with treatment tailored to the specific organism and its susceptibility profile

Fungi

• Prevalence: Uncommon, but cause significant morbidity and mortality
• Characteristics: Often associated with prosthetic valves, IVDU, prolonged antibiotic therapy, and immunocompromised patients
• Types
  • Candida spp.: The most common fungal cause of endocarditis
  • Aspergillus spp.: Less common, but can cause aggressive infections
• Clinical Presentation: Fever, new heart murmur, embolic events. Can have a subacute or chronic course. May be difficult to diagnose
• Treatment: Requires antifungal therapy, often with surgical intervention

Less Common Agents of Endocarditis

• Nutritionally Variant Streptococci (NVS)
  • These are Streptococci that require pyridoxal (Vitamin B6) for growth
  • They are difficult to identify by routine laboratory methods
• Brucella spp.: A zoonotic pathogen; endocarditis is rare but can occur
• Coxiella burnetii: Causes Q fever. Endocarditis can occur years after the initial infection
• Tropheryma whipplei: Causes Whipple’s disease, and endocarditis is a rare manifestation
• Bartonella spp.: Endocarditis is associated with Bartonella, particularly in patients with valvular heart disease
• Chlamydia psittaci: Causes psittacosis (parrot fever), and endocarditis is a rare complication

Additional Considerations

• Culture-Negative Endocarditis
  • In approximately 2.5-31% of cases, blood cultures are negative, despite clinical signs of endocarditis
  • Reasons
    • Antibiotic use before blood cultures
    • Fastidious organisms (e.g., HACEK organisms, Brucella)
    • Non-bacterial causes (e.g., fungal endocarditis, sterile endocarditis)
    • Inadequate blood culture technique
  • Diagnosis: Requires echocardiography and/or other imaging techniques, serological testing, and, in some cases, valve biopsy for definitive diagnosis
• Prosthetic Valve Endocarditis (PVE)
  • A major complication of prosthetic valve replacement
  • Early PVE: Occurs within 60 days of surgery. Staphylococcus aureus and CoNS are the most common causes
  • Late PVE: Occurs >12 months after surgery. Streptococci and Enterococci are more common causes
• Infective Endocarditis (IE) vs. Non-Infective Endocarditis
  • IE is caused by infection, whereas non-infective endocarditis is usually caused by a sterile vegetation

Key Terms

• Endocarditis: Inflammation of the inner lining of the heart (endocardium)
• Vegetation: An accumulation of platelets, fibrin, microorganisms, and inflammatory cells on the heart valves
• Bacteremia: The presence of bacteria in the bloodstream
• Prosthetic Valve Endocarditis (PVE): Endocarditis that occurs in patients with prosthetic heart valves
• Native Valve Endocarditis (NVE): Endocarditis that occurs in patients with their own, natural heart valves
• Staphylococcus aureus: A Gram-positive bacterium that can cause a wide range of infections, including endocarditis
• Coagulase-Negative Staphylococci (CoNS): A group of staphylococci that do not produce coagulase (e.g., Staphylococcus epidermidis)
• Streptococcus viridans group: A group of streptococci that are normal inhabitants of the oral cavity
• Enterococcus spp.: Gram-positive cocci that are common gut flora. E. faecalis and E. faecium are common causes of endocarditis
• HACEK organisms: A group of fastidious Gram-negative bacteria (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae)
• Fungal Endocarditis: Endocarditis caused by fungi (e.g., Candida spp., Aspergillus spp.)
• Embolic Events: Occurrences in which bacteria, fragments of vegetation, or other particles break away from the heart valves and travel through the bloodstream, potentially causing infection in other organs
• Antibiotic Resistance: The ability of bacteria to survive and multiply in the presence of antibiotics
• IVDU: Intravenous drug use
• Surgical Intervention: In endocarditis, this may include valve replacement or repair, debridement of infected tissue, and drainage of abscesses