Infective Endocarditis

Infective endocarditis (IE) is an inflammation of the endothelial lining of the heart muscle, valves and great vessels. The valves have a particularly high propensity for infection due to the lack of blood supply and limited access to immune cells. IE is relatively rare in children. It has an estimated annual incidence of 3 to 9 cases per 100,000 persons in industrialized countries. The highest rates are observed among patients with prosthetic valves, intracardiac devices, unrepaired cyanotic congenital heart diseases, or a history of infective endocarditis. About 50% of cases of infective endocarditis develop in patients with no known history of valve disease. Other risk factors include chronic rheumatic heart disease (which now accounts for <10% of cases in industrialized countries), age-related degenerative valvular lesions, hemodialysis, and coexisting conditions such as diabetes, human immunodeficiency viral infection, and intravenous drug use.

Pathogenesis

Bacteremia and the presence of endothelial damage are important factors in the pathogenesis of IE. Cyanosis and polycythemia, if present, increase the viscosity of the blood and further enhance the likelihood of developing IE. Foreign materials such as prosthetic valves or shunts also significantly increase the risk for developing IE. It is not surprising that cyanotic CHD with an artificial shunt or prosthetic valves constitutes the highest risk for IE.

Neonatal endocarditis frequently occurs on the right side of the heart and is associated with disruption of endocardium or valvular endothelial tissue by catheter-induced trauma in hospitalized infants. Premature neonates often experience transient episodes of bacteremia from trauma to the skin and mucous membranes, vigorous endotracheal suctioning, parenteral hyperalimentation, or placement of umbilical or peripheral venous catheters. The combination of endothelial damage and bacteremia is critical for the induction of IE.

Pathology

Vegetations develop at the site of endothelial damage, which is usually located at the lower pressure side of the lesion i.e. in the right ventricle in patients with VSD and on the atrial surface of the mitral valve with mitral insufficiency.

 After bacteria adhere to the damaged endothelium, platelets and fibrin are deposited over the organisms, leading to the formation of a vegetation. The organisms trapped within the vegetation are protected from phagocytic cells and other host defense mechanisms.

Microbiology

Viridans group streptococcus, enterococci and S. aureus are responsible for most cases of IE. Streptococcus pneumoniae, coagulase negative staphylococcus, gram negative bacilli and fungi may also cause IE. The type of pathogens depends on the following factors: i) whether the valve is a native or a prosthetic valve, ii) patient age and iii) source of infection.

The blood cultures may be negative in patients who have already received antibiotics or in patients who have IE caused by fastidious microorganisms such as petronella species, brucella speciesCoxiella burnetii, bacteria in the HACEK group (haemophilus speciesactinomycetemcomitans, Cardiobacterium hominis,   Eikenella corrodens and  Kingella kingae), and  Tropheryma whipplei. In these cases, serologic testing, blood polymerase chain reaction (PCR) assay and highly specialized microbiologic techniques may lead to the identification of the pathogen in up to 60% of cases.

Clinical presentation

Persistent or recurrent low grade fever is the most common symptom of IE. Other symptoms are nonspecific and include malaise, myalgia, arthralgia, anorexia, night sweats and headaches. Splenomegaly can be found in 15-50% of patients with IE. A new or changing murmur indicates valvular involvement.

The classic peripheral manifestations of IE are rarely seen nowadays. These include petechiae, splinter hemorrhages (hemorrhages in the nail beds), Osler nodules (small, tender nodules on the pads of fingers and toes), Janeway lesions (painless hemorrhages on palms and soles), and Roth spots (hemorrhages in the retina with a white center).

Making the diagnosis

 

The Duke Criteria for diagnosis of infective endocarditis: Requires 2 major + 1 minor OR 1 major + 3 minor OR 5 minor criteria for diagnosis 

Major criteria

Minor criteria

Positive blood Cx for IE

Predisposing heart condition or IV drug use

Typical micro-organism for IE from 2 separate blood Cx 1

Fever > 38° C

Evidence of endocardial involvement2

Vascular phenomena (arterial emboli, septic pulmonary infarcts, conjunctival hemorrhage, intracranial hemorrhage and Janeway lesions)

 

 

Immunologic phenomena (glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor)

 

 

Positive blood Cx but not meeting major criteria

 

 

Echocardiographic findings consistent with IE but not meeting major criteria

 * : Viridans streptococci, Streptococcus bovis and HACEK group OR Staph aureus/enterococci in the absence of a primary focus and persistently positive blood Cx defined as 2 blood Cx drawn 12 hours apart

# : Positive echocardiogram for vegetations OR new valvular regurgitation

Management

The management of IE includes 4-6 weeks of high dose IV antibiotics. The choice of antibiotics depends on the organism isolated and the results of antibiotic sensitivity testing. Initial empiric therapy may be based on the table below. Surgical intervention may be necessary if vegetations are causing obstruction, or if there is significant malfunction of a prosthetic valve.

  

Antibiotic

Dosage

Native valves or prosthetic valves 1 year after surgery

Ampicillin

+

Oxacillin

+

Gentamicin

12 g/day IV in 4-6 doses

 

 12 g/day IV in 4-6 doses

 

 3 mg/kg/day IV in 1 dose

Prosthetic valves within 1 year of surgery

Vancomycin

+

Gentamicin

+

Rifampin

30 mg/kg/day IV in 2 doses

  

3 mg/kg/day IV in 1 dose

 

900-1200 mg IV/PO in 2 or 3 divided doses

 

Antimicrobial prophylaxis: (2007 AHA guidelines)

Antimicrobial prophylaxis is indicated in patients undergoing dental procedures who have:

  1. A prosthetic heart valve
  2. A history of IE
  3. A heart transplant with abnormal heart valve function
  4. CHD only under the following conditions:

a) Unrepaired cyanotic CHD including those with palliative shunts and conduits,
b) Completely repaired CHD with a prosthetic material or device during the first 6 months after the procedure
c) Repaired CHD with a residual defect

Antibiotics are NOT recommended for patients who have procedures involving the reproductive, urinary or gastrointestinal tract.

References

Prevention of Infective Endocarditis.   2007 Guidelines From the American Heart Association.   Circulation. 116:1736-1754.

Ferrieri, P, et al.   Unique Features of Infective Endocarditis in Childhood.   Circulation. 2002;105:2115. Scientific statement from American Heart Association

Hoen BDuval X . Clinical practice. Infective endocarditis. N Engl J Med .  2013 Apr 11;368(15):1425-33