Saturday, February 19, 2011

Infective endocarditis


Infective endocarditis (IE) is defined as inflammation of any of the following:
  • Heart valves.
  • Septal defects.
  • Mural endocardium.
  • Extracardiac sites: A-V shunts, A-A shunts & Coarctation sites.


  • Streptococci (70 % of cases): Streptococcus Viridans alone causes 50 % of all cases, while Streptococcus Fecalis & Streptococcus Pyogenes cause 20 %.
  • Staphylococci (20 % of cases): Staphylococcus Aureus, Coagulase-negative Staphylococci.
  • Other organisms (the remaining 10 %): Pneumococci, Gonococci, Brucella, Clamydia, Rickettsia, Bartonella, Coxiella, Fungi, Viruses.

Streptococcus Viridans alone causes 50 % of all cases of IE.

Portal of entry:
IE either follows provoked or unprovoked bacteremia.
Provoked bacteremia could be due to: Dental work, Surgery, Drug abuse.

Bad teeth, an important source of provoked bacteremia.

Repeated injections in superficial veins in a drug abuser is another source of provoked bacteremia.

Underlying heart disease:

IE usually occurs on top of underlying heart disease, but may occur on top of a normal heart.

Underlying heart disease may include:
  • Rheumatic heart disease:
    • Mitral valve: Atrial surface.
    • Aortic valve: Ventricular surface.
    • Rarely; Tricuspid valve (Drug abusers), Or pulmonary valve.
  • Prosthetic cardiac valves.
  • Congenital heart disease:
    • Ventricular septal defect (VSD): on right ventricular (RV) wall, or on the defect edge.
    • Patent ductus arteriosus (PDA): On pulmonary artery (PA) wall.
    • Coarctation of the aorta: on aortic wall distal to coarctation site.
    • Tetralogy of Fallot.
    • Congenital valvular heart disease: Bicuspid aortic valve, mitral valve prolapse (MVP), pulmonary stenosis (PS).
  • Rare cases: hypertrophic obstructive cardiomyopathy (HOCM), arteriovenous (A-V) and arterioarterial (A-A) shunts, calcified mitral annulus, mural thrombi.

Pathology and clinical picture of IE:

Clinical course:
  • Most cases present as subacute bacterial endocarditis (SBE), and are mostly caused by Streptococcus Viridans.
  • Some cases present as acute endocarditis and are mostly caused by Staphylococcus Aureus, and less commonly Coagulase-negative Staphylococci or Pneumococci.
Infective endocarditis is considered a systemic, not only a cardiac disease.

  • SBE: Low-grade fever, headache, sweating, malaise, loss of weight, and pains in the back, muscles & joints.
  • Acute endocarditis: High-grade fever, profuse sweating, rigors, and commonly CHF. Rapid death may also occur.


General examination:
  • General look: Earthy look, Pallor, Toxic face.
  • Hyperpyrexia.
  • Tachycardia, and other arrhythmia, may occur.
  • Skin:
  • Peticheal hemorrhages: Particularly on the legs & the chest wall
  • Splinter hemorrhages: Under the nails.
  • Osler’s nodes: On pads of fingers & toes, and thenar & hypothenar eminences.
  • Janeway lesions: Hemorrhagic raised lesions in palms & soles.
  • Clubbing of the fingers & toes: In long-standing cases.
  • Absent pulsations (Embolic).
  • Eyes: Subconjunctival hemorrhages, Roth spots (Retinal petichae), Unilateral blindness (embolic).

Splinter hemorrhages.

Osler’s nodes

Janeway lesions.

Clubbing of the fingers.

Sub-conjunctival hemorrhages.

Roth spots.

Cardiac involvement: 

Any of the following may occur:
  • Clinically:
    • Appearance of new murmurs.
    • Change of previous murmurs.
    • Manifestations of CHF.
    • Signs of pericarditis with or without pericardial effusion.
  • Pathology:
    • Endocardial: Vegetations.
    • Myocardial: Myocarditis, abscess, myocardial infarction (MI).
    • Pericardial: Fibrinous or supporative pericarditis with or without effusion.
    • Rupture of: cusps, chordae, and/or papillary muscles.

Infective endocarditis/Vegetations adherent to valve.

Renal involvement: 

Any of the following may occur:
  • Clinically:
    • Sudden pain & tenderness.
    • Hematuria.
    • Renal failure.
  • Pathology:
    • Immunological: Focal glumerulonephritis, Diffuse glumerulonephritis, Proliferative glumerulonephritis.
    • Renal abscess.
    • Renal infarction.

Renal infarction.

Splenic involvement: 

Any of the following may occur:
  • Clinically:
    • Sudden pain & tenderness.
    • Splenic friction rub.
    • Splenomegaly, in long-standing cases.
  • Pathology:
    • Splenic hyperplasia.
    • Splenic infarction.
    • Splenic abscess.
    • Splenic rupture, with peritonitis.

Pulmonary involvement: 

Any of the following may occur:
  • Clinically:
    • Pleural effusion.
    • Pulmonary embolism.
    • Pneumonia.
  • Pathology:
    • Pleurisy with or without effusion.
    • Pulmonary infarction.
    • Pulmonary consolidation.
    • Lung abscess.

CNS involvement: 

Any of the following may occur:
  • Clinically:
    • Meningo-encephalitis.
    • Increased intra-cranial tension.
    • Neurological deficits.
  • Pathology:
    • Diffuse inflammation.
    • Brain abscess.
    • Mycotic aneurysm.
    • Cerebral infarction.
    • Cerebral hemorrhage.

Systemic vessels: 

Manifestations will differ according to the site, e.g. peripheral, cerebral, abdominal…etc, and any of the following may occur:
  • Embolism.
  • Mycotic aneurysm.

Mycotic aneurysms.

Musculoskeletal manifestations: 

Any of the following may occur:
  • Arthralgia.
  • Arthritis.
  • Low back pain.
  • Diffuse myalgia.

Pathogenesis of the manifestations of IE:

Manifestations of infective endocarditis may be the result of:
  • Direct effects of the organisms, e.g.
    • Cardiac vegetations & intra-cardiac destruction.
    • Mycotic aneurysms.
    • Abscesses.
  • Embolization.
  • Immunological responses, e.g.
    • Osler’s nodes.
    • Roth spots.
    • Glumerulonephritis.
    • Dysglobulinemia.

Septic emboli with hemorrhage and infarction due to acute Staphylococcus Aureus endocarditis.

Laboratory investigations:
  • Complete blood count (CBC) may reveal: Normocytic normochromic anemia, Leukocytosis, High ESR.
  • Serum proteins analysis may reveal: Dysglobulinemia, Hyperglobulinemia, Abnormal globulins, False positive rheumatoid factor.
  • Urine analysis may reveal: Microscopic hematuria.

Blood culture:

Culture of the causative organisms from the patient’s blood is the mainstay and the single most important laboratory test performed in the diagnosis of infective endocarditis.

At least 3 blood culture sets should be obtained in the first 24 hours. More specimens may be needed if the patient has received antibiotics in the preceding 2 weeks.

In about two thirds of the cases, all blood specimens yield positive results on culture.

False negative blood cultures may occur in 3 - 23% of cases, which may be due to:
  • Prior antibiotic therapy in the preceding 2 weeks.
  • Special organisms: e.g. Clamydia, Bartonella, Coxiella, fungi, viruses…etc.
  • Non-infective endocarditis: e.g. Sterile thrombotic endocarditis.

Electrocardiogram (ECG) may show:
  • First-degree heart block.
  • Complete heart block.
  • Bundle branch blocks.

Echocardiography may show:
  • Vegetations.
  • Abscesses.
  • Underlying heart disease.


Diagnostic criteria:
(Source: Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633รข€“638).

Major criteria:

  • Blood culture positive for IE:
    • Typical microorganisms consistent with IE from two separate blood cultures:
      • Viridans streptococci, Streptococcus bovis, Hacek group, S. aureus; or
      • Community-acquired enterococci, in the absence of a primary focus; or
    • Microorganisms consistent with IE from persistently positive blood cultures, defined as follows:
      • At least two positive cultures of blood samples drawn >12 h apart; or
      • All of three or a majority of 4 separate cultures of blood (with first and last sample drawn at least 1 h apart).
    • Single positive blood culture for Coxiella burnetii or antiphase I IgG antibody titer >1:800.
  • Evidence of endocardial involvement:
    • Echocardiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least possible IE by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients), defined as follows:
    • Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or Abscess; or New partial dehiscence of prosthetic valve.
    • New valvular regurgitation (worsening or changing of preexisting murmur not sufficient).

Minor criteria:

  • Predisposition, predisposing heart condition or.
  • Fever >38°C.
  • Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions.
  • Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor.
  • Microbiological evidence: positive blood culture, but does not meet a major criterion as noted above or serologic evidence of active infection with organism consistent with IE.

Definite IE is considered in the presence of:
  • Pathologic criteria:
    • Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or
    • Pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis
  • Clinical criteria:
    • Two major criteria; or One major criterion and three minor criteria; or Five minor criteria.

Possible IE is considered in presence of:
  • One major criterion and one minor criterion; 
  • or Three minor criteria.

Diagnosis of IE is rejected in the following cases:
  • Firm alternate diagnosis explaining evidence of infective endocarditis; or
  • Resolution of infective endocarditis syndrome with antibiotic therapy for 4 days; or
  • No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for 4 days; or
  • Does not meet criteria for possible infective endocarditis, as above.

Management of IE:

Management may include one or more of the following:
  • Antibiotic therapy.
  • Surgery.
  • Management of complications.
  • Management of the underlying heart disease.
  • Prophylaxis.

Antibiotic therapy:

Antibiotics should be administered in a dosage designed to give sustained bactericidal serum concentrations throughout much or the entire dosing interval.

The first step is to define the organism in the blood, if possible, by gram stain. This will help empirical choice of antibiotics.

Culture & sensitivity tests are then performed. Their results may dictate modification of the antibiotic regimen.

When sensitivity results are available:
  • If the response to empirical antibiotic regimen is adequate: It should be continued regardless of the sensitivity results.
  • If the response is inadequate: antibiotics should be modified according to sensitivity results.

If the kidney function is impaired:
Gentamycin doses should be modified accordingly: 80 mg doses are used, but the interval between doses are calculated as: Interval = serum creatinine x 8.


Any of the following may be needed:
  • Surgery for control of infection.
  • Surgery for complications.
  • Surgery for the underlying heart disease.

Prophylaxis against IE:

Older guidelines recommended the following:
Indications for prophylaxis:
  • Endocarditis prophylaxis recommended:
    • High risk:
      • Prosthetic cardiac valves, including bioprosthetic and homograft valves
      • Previous bacterial endocarditis, even in the absence of heart disease
      • Complex cyanotic congenital heart disease (e.g., single ventricle states, transposition of the great arteries, tetralogy of Fallot).
      • Surgically constructed systemic-pulmonary shunts or conduits.
    • Moderate risk:
      • Rheumatic and other acquired valvular dysfunction, even after valvular surgery.
      • Hypertrophic cardiomyopathy.
      • Mitral valve prolapse with valvular regurgitation and/or thickened leaflets.
      • Most other congenital cardiac malformations (other than the above and below).
  • Endocarditis prophylaxis not recommended:
    • Isolated secundum atrial septal defect.
    • Surgical repair without residua beyond 6 mo of secundum atrial septal defect, ventricular septal defect, and patent ductus arteriosus.
    • Previous coronary artery bypass graft surgery.
    • Mitral valve prolapse without valvular regurgitation.
    • Physiologic, functional, or innocent heart murmurs.
    • Previous Kawasaki disease without valvular dysfunction.
    • Previous rheumatic fever without valvular dysfunction.
    • Cardiac pacemakers and implanted defibrillators.

The new guidelines show taking preventive antibiotics is not necessary for most people and, in fact, might create more harm than good: Unnecessary use of antibiotics could cause allergic reactions and dangerous antibiotic resistance.

Only the people at greatest risk of bad outcomes from infective endocarditis — an infection of the heart's inner lining or the heart valves — should receive short-term preventive antibiotics before common, routine dental and medical procedures.

Patients at the greatest danger of bad outcomes from IE and for whom preventive antibiotics are worth the risks include those with:
  • artificial heart valves.
  • a history of having had IE
  • certain specific, serious congenital (present from birth) heart conditions, including:
  • unrepaired or incompletely repaired cyanotic congenital heart disease, including those with palliative shunts and conduits
  • a completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter interventions, during the first six months after the procedure.
  • any repaired congenital heart defect with residual defect at the site or adjacent to the site of a prosthetic patch or prosthetic device
  • a cardiac transplant which develops a problem in a heart valve.

Several protocols are suggested for the empirical choice of antibiotics; a simplified protocol is suggested here:

For dental work:
  • If no prosthetic valve & no past history of endocarditis:
    • Amoxicillin 2gm, po, 1h before procedure
    • Then: 500 mg, po, 6h later
  • In presence of prosthetic valves and/or past history of endocarditis:
    • Amoxicillin 1gm, iv / im + Gentamycin 80mg, iv / im, just before procedure
    • Then: Amoxicillin 500 mg, po, 6h later.

For pulmonary procedures:
  • If no prosthetic valve & no past history of endocarditis:
    • Amoxicillin 1gm, iv / im, just before surgery
    • Then: 500 mg, po, 6h later
  • In presence of prosthetic valves and/or past history of endocarditis:
    • Amoxicillin 1gm, iv / im + Gentamycin 80mg, iv / im, just before surgery
    • Then: Amoxicillin 500 mg, po, 6h later.

For genitourinary surgery:
  • Amoxicillin 1gm, iv / im + Gentamycin 80mg, iv / im, just before surgery;
  • Then: Amoxicillin 500 mg, po, 6h later.

In all cases, if there is allergy to Penicillin derivatives,
  • Oral Amoxycillin is replaced by oral Erythromycin 500 mg.
  • And parenteral Amoxycillin is replaced by iv Vancomycin 500 mg.

Prognosis of IE:

High morbidity and mortality are still encountered despite improvements in diagnosis and treatment due to the increasingly complex situations, e.g. older ages, infected prosthetic valves or congenital heart disease, and the increasing cases of acute IE caused by Staphylococcus Aureus.

1 comment:

jade89 said...

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