Infective Endocarditis

• Infective endocarditis refers to microbial infection of the endocardial surface (endocardium) of the heart.
• Considerable cause of morbidity and mortality in children with underlying heart disease.
• Is one of the most dreaded complications of structural heart disease.

• The estimated incidence in children was 0.3 per 100,000 children per year with a mortality of 11.6%.
• There has been an increase in the incidence in the developed world of recent years resulting from:
  • Increased survival of patients with cardiovascular disease,
  • Advances in surgical and medical approaches to congenital heart disease (CHD) during the past several decades,
  • Aggressive treatment regimens in neonatal and pediatric intensive care units.
• Whereas rheumatic heart disease was a major underlying cardiac condition in U.S. children with endocarditis until the 1970s, it has become an unusual underlying cardiac condition in more recent years. This is not true in developing countries, where endocarditis remains an important complicating factor in individuals with rheumatic heart disease.
• CHD most associated with infective endocarditis include:
  • Tetralogy of Fallot,
  • Ventricular septal defect,
  • Patent ductus arteriosus,
  • Aortic valve abnormalities.
• Previous corrective or palliative surgery for CHD, with or without implanted vascular grafts, patches, or prosthetic cardiac valves, and various reports have indicated that 50% to 70% of children with CHD have had previous cardiac surgery.
• Neonates: Most cases occur in structurally normal hearts. It is relatively uncommon.
• Patients with underlying cardiovascular disease may develop endocarditis at any age in childhood, adolescence, or adulthood.

• Acute vs subacute
• Native valve vs prosthetic valve
• Based on organism:
  • Viral
  • Bacterial
  • Fungal

• A wide variety of organisms are associated with infective endocarditis, but most commonly:
  • Viridans streptococci (S. mutans, S. mitis, S. sanguis)
  • Staphylococcus aureus
  • Group D Streptococci (Enterococcus)
• These are responsible for 60% of cases of IE.
• Other organisms (Native valve):
  • Coagulase negative staphylococci
  • Other streptococci
  • HACEK
  • Pseudomonas
  • Coxiella burnetii
  • Brucella
  • Chlamydia spp
  • Neisseria gonorrheae
  • Legionella
  • Bartonella
  • Campylobacter
  • Pasteurella multocida
• Prosthetic valve:
  • Staphylococcus epidermidis
  • Staphylococcus aureus
  • Viridans group streptococcus
  • Pseudomonas aeruginosa
  • Serratia marcescens
  • Diphtheroids
  • Legionella species
  • HACEK group
  • Fungi (Candida, Aspergillus, Torulopsis glabrata)

• Risk factors:
  • Underlying congenital heart disease
  • Rheumatic heart disease
  • Valvular abnormalities
  • Prosthetic valves
  • Intravenous drug abusers
  • Indwelling devices
  • Immunosuppression
  • Dental / gastrointestinal / urinary procedures
  • Poor oral hygiene
• Two fundamental requirements:
  • Bacteremia
  • Endocardial damage/injury
• The presence of structural abnormalities of the heart or great arteries, with a significant pressure gradient or turbulence, produces endothelial damage.
• Such endothelial damage induces thrombus formation with deposition of sterile clumps of platelet and fibrin (nonbacterial thrombotic endocarditis), which provides a nidus for bacteria to adhere and eventually form an infected vegetation.
• Platelets and fibrin are deposited over the organisms, leading to enlargement of the vegetation.

Nonbacterial Thrombotic Endocarditis

• Endothelial injury
• Hypercoagulable state
• Platelet-fibrin thrombi
• Lesions seen at coaptation points of valves:
  • Atrial surface mitral/tricuspid
  • Ventricular surface aortic/pulmonic
• Modes of endothelial injury:
  • High velocity jet
  • Flow from high pressure to low pressure chamber
  • Flow across narrow orifice of high velocity
• Bacteria deposited on edges of low pressure sink or site of jet impaction

Conversion of NBTE to IE

• Frequency & magnitude of bacteremia
• Density of colonizing bacteria:
  • Oral > GU > GI
• Disease state of surface:
  • Infected surface > colonized surface
• Extent of trauma
• Resistance of organism to host defenses
• Most aerobic gram negatives susceptible to complement-mediated bactericidal effect of serum
• Tendency to adhere to endothelium:
  • Dextran producing strep
  • Fibronectin receptors on staph, enterococcus, strep, Candida

• Clinical manifestations:
  • Direct:
    • Constitutional symptoms of infection (cytokine)
  • Indirect:
    • Local destructive effects of infection
    • Embolization – septic or bland
    • Hematogenous seeding of infection:
      • N.B. may present as local infection or persistent fever; metastatic abscesses may be small, miliary
    • Immune response:
      • Immune complex or complement-mediated
• Local destructive effects:
  • Valvular distortion/destruction
  • Chordal rupture
  • Perforation/fistula formation
  • Paravalvular abscess
  • Conduction abnormalities
  • Purulent pericarditis
  • Functional valve obstruction
• The immediate consequences of endocarditis include:
  • Vegetation formation
  • Hemodynamic alterations
  • The clinical syndrome
• Many important extracardiac manifestations in endocarditis are related to immunologic mechanisms.
• Rheumatoid factor is present for 6 weeks or longer in sera of about half of the patients with endocarditis. This is considered to be due to a gradual hyperimmunization of the host.
• Another immunologic sequela of endocarditis is the presence of circulating immune complexes in the sera of patients.
• The kidney is an extracardiac site frequently affected in patients with endocarditis. Microscopic and macroscopic emboli are the most frequently described noncardiac pathologic lesions.
• However, abscess formation has also been reported following septic embolization to the kidney.
• The nephritis seen in patients with endocarditis may manifest itself microscopically as either focal or diffuse glomerulonephritis.

History

• Most patients have a history of an underlying heart defect.
• However, some patients with bicuspid aortic valve may not have been diagnosed with the defect before the onset of the endocarditis.
• A history of a recent dental procedure or tonsillectomy is occasionally present, but a history of toothache (from dental or gingival disease) is more frequent than a history of a procedure.
• Endocarditis is rare in infancy; at this age, it usually follows open-heart surgery.
• The onset is usually insidious with prolonged low-grade fever and somatic complaints, including:
  • Fatigue
  • Weakness
  • Loss of appetite
  • Pallor
  • Arthralgia
  • Myalgias
  • Weight loss
  • Diaphoresis

Physical Examination

• Heart murmur is universal (100%):
  • The appearance of a new heart murmur and an increase in the intensity of an existing murmur are important.
• Fever is common (80% to 90%). The temperature fluctuates between 38.3°C and 39.4°C.
• Splenomegaly is common (70%).
• Skin manifestations (50%) (either secondary to microembolization or as an immunologic phenomenon) may be present in the following forms:
  • Petechiae on the skin, mucous membranes, or conjunctivae are the most frequent skin lesions.
  • Osler's nodes (tender, pea-sized red nodes at the ends of the fingers or toes) are rare in children.
  • Janeway's lesions (small, painless, hemorrhagic areas on the palms or soles) are rare.
  • Splinter hemorrhages (linear hemorrhagic streaks beneath the nails) are also rare.

Clinical Features

• Embolic or immunologic phenomena in other organs are present in 50% of cases:
  • Pulmonary emboli may occur in patients with VSD, PDA, or a systemic-to-PA shunt.
  • Seizures and hemiparesis are the result of embolization to the central nervous system (20%) and are more common with left-sided defects such as aortic and mitral valve disease or with cyanotic heart disease.
  • Haematuria and renal failure may occur.
  • Roth's spots (oval, retinal hemorrhages with pale centers located near the optic disc) occur in less than 5% of patients.

Clinical Features

• Carious teeth or periodontal or gingival disease is frequently present.
• Clubbing of fingers in the absence of cyanosis develops rarely in more chronic cases.
• Signs of heart failure may be present as a complication of the infection.

IE in Neonates

• The clinical manifestations in a neonate with IE are nonspecific (such as respiratory distress, tachycardia) and may be indistinguishable from septicemia or congestive heart failure (CHF) from other causes.
• Embolic phenomena (such as osteomyelitis, meningitis, pneumonia) are common.
• There may be neurologic signs and symptoms (such as seizures, hemiparesis, apnea).

• Blood culture: Positive in 90% of cases without antibiotic use and 50-60% with antibiotic use.
  • Maximise yield by:
    • Taking three cultures within the first 24 hours
    • Taking cultures at the same or different site
    • If negative in 48 hours, take another two
    • Cultures should be taken before commencement of antibiotics, if possible
    • Taking 1-3ml in young children and 5-7ml in older children
    • Aerobic cultures should be performed, taking note of requirements for fastidious organisms
• Echocardiography:
  • TTE has become an extremely valuable tool in the evaluation for IE. TEE may be more sensitive.
  • Suggestive findings include:
    • Vegetations
    • Valvular dysfunction
    • Perivalvular extension including abscesses
    • Underlying heart disease
• Other investigations:
  • Full blood count:
    • Hb < 12g/dl
    • Leucocytosis with a left shift
    • Platelets may be low or normal
  • Raised acute phase reactants
  • Urinalysis: Microscopic haematuria

Modified Duke’s Criteria

• Definite IE
• Possible IE
• Rejected IE

Definite IE

• Pathologic criteria:
  • Micro-organisms demonstrated by culture or histologic examination of a vegetation
  • Pathological lesions: vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis

Major Criteria

1. Blood culture positive for infective endocarditis (IE):
   • Typical micro-organisms consistent with IE from 2 separate blood cultures
   • Micro-organisms consistent with IE from persistently positive blood cultures defined as follows:
     • At least 2 positive cultures of blood samples drawn >12 h apart; or
     • All of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 h apart)
   • Single positive blood culture for Coxiella burnetii
2. Evidence of endocardial involvement:
   • Echocardiogram positive for IE defined as follows:
   • New valvular regurgitation (worsening or changing or pre-existing murmur not sufficient)

Minor Criteria

1. Predisposition, predisposing heart condition, or injection drug use
2. Fever, temperature >38°C
3. Vascular phenomena
4. Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor
5. Microbiologic evidence: positive blood culture, but does not meet a major criterion as noted above

Diagnosis

• Definite IE
• 2 major OR
• 1 major + 3 minor OR
• 5 minor

Possible IE:

• 1 major + 1 minor OR
• 3 minor