endocarditis

Etiology

• common microbiologic causes (see common organisms by study)
  • native valve
    • Streptococci
      • Streptococcus viridans with bicuspid aortic valve, mitral valve prolapse
    • Staphylococci (S aureus most common cause)
    • Gram-negative rods
  • prosthetic valve & IV drug abuse
    • Staphylococci
    • Streptococci & Enterococci
    • Gram-negative rods
    • fungi
• specific mediators of bacterial adherence influence likelihood of bacteremic organism's attachment to cardiac valve
• uncommon microbiologic causes
  • HACEK bacterial group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)
  • anaerobes
  • Chlamydia
  • Rickettsia
  • Brucella
  • Legionella
  • Coxiella
  • viruses
    • echovirus
    • coxsackie virus
      • adenovirus
• culture negative infectious endocarditis (3-5%)
  • prior antibiotics
  • fastidious organisms
  • viral or fungal etiology
  • indolent tricuspid valve disease
• non infectious thrombotic endocarditis
  • systemic lupus erythematosus (Libman-Sacks endocarditis)
• risk factors for endocarditis
  • prosthetic heart valve*
  • congenital heart disease: Tetralogy of Fallot
  • rheumatic heart disease
  • mitral valve prolapse with regurgitation
  • bicuspid aortic valve
  • prior endocarditis*
  • Marfan's syndrome
  • valvular stenosis
  • valvular insufficiency
  • hypertrophic cardiomyopathy
  • intravenous drug abuse (IVDA)
  • central venous catheters
  • hemodialysis catheters & shunts
  • wires from pacemakers & implantable defibrillators
  • recent dental work or surgery
  • older age
• endocarditis is much more likely to result from regular bacteremia from daily activities than from bacteremiaduring dental procedures, gastrointestinal or urogenital procedures

* high-risk of endocarditis

Epidemiology

• mean age of patients is > 50 years
• more restrictive antibiotic prophylaxis recommendations & practices have not led to an increase in endocarditis

Pathology

• cardiac complications
  • valve-ring abscess
  • valvular perforation
  • valvular rupture
  • myocardial abscess
  • valvular stenosis secondary to large vegetations
  • systemic embolization
  • mycotic aneurysms
• kidney complications (common)
  • renal abscess
  • renal embolization & infarction
  • glomerulonephritis
• CNS involvement
  • ischemic stroke secondary to cardiac emboli
  • cerebral vasculitis
  • meningitis
  • cerebral abscess
  • subarachnoid hemorrhage due to ruptured mycotic aneurysm
• affected valves:
  • single valve involvement
    • mitral > aortic > tricuspid > pulmonic
  • involvement of right & left heart valves (3-5%)
  • involvement of both aortic & mitral valves (30-35%)
  • heroin associated with right-sided endocarditis
• mitral valve endocarditis is generally associated with mitral regurgitation

Clinical manifestations

• protean manifestations due to:
  • cardiac complications of valvular dysfunction
  • bacteremia
  • bland or septic emboli
  • circulating immune complexes
• common manifestations
  • fever/chills (90-95%)
  • bacteremia
  • malaise
  • heart murmur (> 80%)
  • embolic phenomena - focal neurologic signs
  • congestive heart failure
  • cough, pleuritic chest pain & pneumonia more common in right-sided endocarditis (IV drug abuse)
• uncommon manifestations
  • splenomegaly
  • retinal lesions (Roth spots)
  • meningitis
  • cutaneous manifestations
    • splinter hemorrhages
    • Osler's nodes
    • Janeway lesions
    • petechiae
  • hematuria
• mitral valve endocarditis generally results in a holosystolic murmur best heard at the cardiac apex due to mitral regurgitation

Diagnostic criteria

• Duke criteria for diagnosis of infectious endocarditis

Laboratory

• complete blood count (CBC)
  • normocytic anemia
  • leukocytosis
  • monocytosis (< 25%)
• urinalysis (abnormal < 65%)
  • proteinuria
  • pyuria
  • hematuria
• blood cultures (positive in > 93%)
  • if blood cultures negative, consider culture-negative endocarditis
• antibiotic sensitivities
  • determination of the minimum inhibitory (MIC) & minimum bactericidal concentration (MBC)
  • assess aminoglycoside synergy for penicillin-resistant streptococci & enterococci
  • Schlicter test
• erythrocyte sedimentation rate (ESR) increased in > 90%
• see ARUP consult

Diagnostic procedures

• electrocardiogram (ECG)
  • may show conduction abnormalities
  • conduction abnormalities suggest extension of infection into perivalvular tissue
• echocardiogram
  • transthoracic echocardiogram (TTE)
    • initial imaging test in most clinical situations
    • all septic or bacteremic patients
    • TTE with lower sensitivity than TEE, but better specificity
  • transesophageal echocardiogram (TEE)
    • initial test of choice in patients with moderate to high probability of endocarditis; maybe not
    • septic or bacteremic patients with negative transthoracic echocardiogram
    • better sensitivity than transthoracic echo, but higher incidence of false positives
    • patients with prosthetic valves
    • perivalvular abscess
      • new onset cardiac conduction defect may be clue
    • intracardiac device leads present
    • if transthoracic echocardiogram negative & blood cultures negative, consider transthoracic echocardiogram for culture-negative endocarditis
  • role of echocardiography in assessing prognosis or need for surgery is controversial
• colonoscopy to assess colon cancer in patients with blood cultures positive for:
  • Streptococcus gallolyticus (Streptococcus bovis)
  • Clostridium septicum

Radiology

• chest X-ray may show multiple bilateral small nodules
• multislice computed tomography (CT) may be alternative to TEE

Complications

• embolic strokes are common with left-sided endocarditis, but often clinically silent
  • vegetation size > 10 mm associated with increased risk of embolism & mortality
• severe aortic regurgitation with acute heart failure & pulmonary edema
  • urgent aortic valve replacement
• in-hospital or 14.7% & 1-year mortality of 23.2% when associated with cardiac device (pacemaker, mechanical valve)

Management

• antibiotic therapy
  • empiric therapy (after obtaining blood cultures) if clinical suspicion for endocarditis is intermediate or high
    • community-acquired endocarditis
      • vancomycin plus gentamicin, or
      • ampicillin sulbactam (Unasyn) plus gentamicin
    • nosocomial endocarditis
      • vancomycin, gentamicin + rifampin (S epidermidis) + carbapenem or cefepime (gram-negative baccilli)
    • prosthetic valve endocarditis
      • vancomycin, gentamicin + rifampin
  • general considerations
    • 4-6 weeks duration of intravenous therapy*
      • oral antibiotics after 10 days of IV therapy may be an option
      • oral linezolid or TMP-SMX non-inferior to IV vancomycin
    • PICC line vs internal jugular catheter
    • use of synergistic combinations of antibiotics
    • selection of antibiotic(s) on the basis of an isolated organism (see laboratory)
    • recognition of indications for surgical management
    • switching to oral antibiotics after at least 10 days of IV antibiotics in stable patients not associated with delayed treatment failure
  • specific organisms
    • Streptococcus
      • penicillin-sensitive (MIC < 0.2 ug/mL)
        • penicillin G 10-20 million units IV QD for 4 weeks +/- 2 weeks of gentamicin 1 mg/kg IV every 8 hours
        • vancomycin 15 mg/kg IV every 12 hours for 4 weeks
      • penicillin-resistant (MIC > 0.5 ug/mL)
        • penicillin G 20 million units IV QD plus gentamicin 1 mg/kg every 8 hours for 6 weeks
        • ampicillin 2 g IV every 6 hours plus gentamicin 1 mg/kg every 8 hours for 6 weeks
        • vancomycin 15 mg/kg IV every 12 hours plus gentamicin 1 mg/kg every 8 hours for 6 weeks
    • Enterococcus
      • ampicillin + high-dose ceftriaxone
      • linezolid + high-dose daptomycin +/- beta-lactam for Enterococcus resistant to penicillin, aminoglycosides & vancomycin
    • Staphylococcus
      • add rifampin for prosthetic valve endocarditis
      • gentamicin for 2 weeks for prosthetic valve endocarditis
        • gentamicin no longer considered for native valve S aureus endocarditis
      • MSSA: nafcillin 1.5-2.0 g IV every 4 hours for 4-6 weeks
        • uncomplicated right-sided native value MSSA endocarditis can be treated with 2 weeks of IV nafcillin
      • MRSA: vancomycin 15 mg/kg IV every 12 hours plus rifampin 300 mg PO every 12 hours for 4-6 weeks
        • area under the curve (AUC) to minimum inhibitory concentration (MIC) AUC/MIC should be used to guide therapy
        • AUC/MIC target is 400-600 mg*hour/L assuming MIC <= 1 ug/mL
      • cephalothin 2 gm IV every 6 hours for 4-6 weeks
      • daptomycin is an alternative agent for treating MSSA or MRSA
    • Enteric gram-negative bacilli (E coli, Klebsiella, Proteus, Pseudomonas, Serratia)
      • cephalosporin or broad-spectrum penicillin plus an aminoglycoside determined by antibiotic sensitivityfor 6 weeks
      • left-sided endocarditis due to Pseudomonas or Serratia may require combined medical & surgical intervention
    • fungal
      • prognosis poor
      • antifungal agents with poor activity
  • prosthetic valve
    • Staphylococcus aureus & epidermidis, diphtheroids
      • vancomycin + gentamicin + cefepime
      • vancomycin + gentamicin + rifampin
      • nafcillin + gentamicin
    • Candida or aspergillus
      • amphotericin B + 5-FC + surgery consult
• indications for surgery
  • hemodynamic instability
    • surgery should not be delayed while active infection is treated
  • acute heart failure or progressive congestive heart failure
  • recurrent embolization
  • antibiotic-refractory disease
    • persistent bacteremia or fever > 5-7 days on appropriate antibiotics
      • aortic regurgitation resulting from structural damage to the aortic valve requires aortic valve replacement vs removal of vegetation
  • extension of infection into perivalvular tissue
    • extravalvular intracardiac abscess (ring abscess or aortic abscess)
    • heart block not present prior to endocarditis
    • destructive or penetrating lesion
    • urgent surgery, do not wait 6 weeks
  • mycotic aneurysm
  • any treatment failure with prosthetic valve endocarditis
  • prosthetic valve endocarditis caused by fungi, Pseudomonas aeruginosa or Staphylococcus aureus
  • left-sided endocarditis due to Staphylococcus aureus, fungus, or other resistant organism
  • severe cardiac valvular dysfunction identified by echocardiography
• surgical management
  • valve replacement if structural damage to valve
    • heart failure due to endocarditis indicates structural damage to valve
      • aortic regurgitation
• see prophylaxis for bacterial endocarditis

* special case of right-sided endocarditis caused by methicillin-sensitive S. aureus may be treated by 2 weeks of IV nafcillin + an aminoglycoside

Comparative biology

• combination of aspirin & ticlopidine reduces incidence of both streptococcal & staphylococcal endocarditis in rats
  • abciximab (ReoPro) is also effective in rats

More general terms

• valvular heart disease
• carditis

More specific terms

• culture-negative endocarditis
• Libman-Sacks endocarditis
• marantic endocarditis; non-bacterial thrombotic endocarditis

Additional terms

• antibiotic prophylaxis for bacterial endocarditis
• Duke criteria for diagnosis of infectious endocarditis
• empiric antibiotic therapy
• etiology of bacterial endocarditis, common organism
• Janeway spot or lesion (smoke ring)
• Osler's node
• Slichter test