Infective Endocarditis

Introduction

Bacterial infections can cause serious cardiac disease. Two examples are endocarditis and rheumatic fever. Bacterial endocarditis occurs when certain bloodborne bacteria lodge on damaged endocardial surfaces of the heart usually an abnormal valve or on the anatomic cardiac defect.

The epidemiological pattern of endocarditis has changed significantly during the last few years. The term "infective endocarditis" popularized by Lerner and Weinstein¹ has gained general acceptance in recent medical literature replacing the older term "subacute bacterial endocarditis." The disease was known as acute or subacute depending on the virulence of the organism. But now it is known that organisms with low virulence can produce acute disease and that virulent organisms may produce subacute disease. Factors that contributed to the changing pattern include longer survival of infants and children with congenital heart disease, the widespread use of anti-microbial agents, increased use of indwelling intravenous catheters in intensive care units. The number of children hospitalized with infective endocarditis is reported at 0.55/1000 hospital admissions.

Predisposing Factors

The cardiac lesions that predispose to endocarditis are those that result in high-velocity turbulent flows leading to eddy currents and/or denudation of endocardial epithelium. The rheumatic valvular disease and congenital heart disease still continue to be a major predisposing factor in India. Few cases of endocarditis continue to occur in children with no apparent preexisting heart lesions.

Endocarditis is preceded by bacteremia, often caused by dental or other surgical procedures. The cyanotic patients with dental caries and periodontal disease are, particularly at risk.

Bacteremia and endocardial colonization may be associated with procedures such as hemodialysis via arteriovenous fistula, barium enemas, intravenous alimentation, cardiac catheterization and can also occur following open-heart surgery.

Endocarditis and Specific Heart Disease

In patients with rheumatic heart disease, the mitral valve is the most common site of involvement with an incident of 30-50%. The aortic valve is involved in 5-35% and both valves in about 35%.

Tetralogy of Fallot is the most common lesion associated with endocarditis. Children with small VSD (high-velocity turbulent shunt flow) and patent ductus arteriosus are next to develop infective endocarditis. Endocarditis is also common in children with bicuspid aortic valve, aortic stenosis, and prolapsed mitral valve syndrome. It is very rare with ASD (OS) and pulmonic stenosis.

Children who undergo palliative cardiac surgery with prosthetic material for repair and in whom aortic valvulotomy has been performed continue to be at risk even after successful surgery.

Microbiology

Alpha hemolytic streptococci (Streptococcus viridans) continue to be the most common cause of infective endocarditis in children and adults occurring in 50-60% of patients followed by staphylococcal endocarditis. Streptococcus viridans endocarditis usually follows dental procedures whereas staphylococcal endocarditis is typically associated with cardiac surgery, prosthetic valves and materials, drug addiction, and endocarditis without preexisting heart disease.

Group D streptococci, now called enterococci accounts for less than 4% of endocarditis in children. Pneumococci, Gm-ve bacilli such as Escherichia coli, salmonella are uncommon causes. Fungi, especially candida, are not uncommon especially in patients with compromised host resistance.

The histopathologic hallmark of endocarditis is the vegetation, an amorphous clot typically harboring micro-organisms but scant inflammatory cells. The observation that organisms buried in the vegetation are protected from host defenses explains why long courses of bactericidal antibiotics are needed for reliable cure of endocarditis. In 14-30% of patients, blood culture will remain negative but does not appear to be related to prior antibiotic therapy, duration of the disease, or specific cardiac lesion.

Clinical Features

The classic tetrad of the clinical features of endocarditis is:

• Features of infection

• Features of heart disease

• Features of embolism

• Features of immunological disease

Fever (96-100%) with rigors, sweats, lassitude, arthralgia, myalgia are features of infection. Splenomegaly is present in 60% of the patients and anemia in 100% of patients.

The majority will reveal signs of pre-existing valvar or shunt lesions (85%). The sudden occurrence of aortic insufficiency or mitral insufficiency arises because of the destruction of valve leaflets by the infected vegetations.

Finger clubbing may develop in cyanotic lesions or may already be present in cyanotic heart disease. Hepatomegaly and other signs of heart failure may be present.

Any child with unexpected embolism should be suspected of having endocarditis. The brain, kidneys, liver, spleen, and bones are particular sites for emboli.

Many classic signs of endocarditis, which were previously thought to embolic, are now known to represent an immunological phenomenon. The mechanism of these features is thought to be antigen-antibody complement complexes being deposited in tissues. These features are:

• Splinter hemorrhages, which are linear subungual hemorrhages present on fingers and toes.

• Petechial lesions with the pale center, found in conjunctiva oral mucosa, dorsum of hands, and the trunk.

• Osler's nodes: Uncommon in children. They are painful, small, red, or purple raised lesions found on the pulp of the terminal phalanges of the fingers.

• Janeway lesions: They are flat, non-tender erythematous lesions on the thenar or hypothenar eminences.

• Roth's spots are while centered hemorrhages on the retina.

• A diffuse glomerulonephritis leading to microscopic hematuria with changes identical to proliferative glomerulonephritis.

Diagnosis

Infective endocarditis should be suspected in any child who presents with fever of unknown origin, heart murmur, and splenomegaly.

A positive blood culture confirms the diagnosis. Bacteremia in endocarditis is continuous and not related to temperature spikes hence timing of collection of blood for cultures is not necessary. If six blood cultures are taken within 24 hours, positivity will be 90%. In strongly suspected cases of endocarditis, if routine blood culture fails to grow, the microbiology laboratory should be notified to incubate cultures for 2 or more weeks.

Cardiac patients with prolonged fever of undetermined origin and negative blood culture should probably be treated as having infective endocarditis.

The most common hematological abnormality is normochromic, normocytic anemia of chronic disease reflecting the chronic inflammatory nature of the process. The leukocytosis is a common but variable finding. ESR and CRP (C reactive protein) are always elevated at presentation. Hematuria results from an embolization in renal arteries. Serum globulins are increased and the rheumatoid factor is elevated in 20% of patients.

Echocardiography has been successfully utilized to visualize endocardial vegetations larger than 2 mm and for the non-invasive hemodynamic evaluation of cardiac lesions.

X-Ray chest reveals findings compatible with pre-existing heart disease. Cardiomegaly is present if the patient has congestive heart failure. On occasions, evidence for pericardial effusion will be present.

Prophylaxis And Prevention

Successful prevention of infective endocarditis depends upon several factors including close medical supervision and follow up, avoidance of risk factors, proper dental hygiene, and prophylactic use of antibiotics during surgical procedures especially dental extraction and operative procedures of oropharynx, gastrointestinal or genitourinary tract.

Treatment

The successful treatment of IE has 2 major goals:

• To eradicate microorganisms.

• To correct or at least limit the cardiac and the extracardiac complications caused by infection.

The choice of the proper antibiotic is necessary because the organisms are located within the vegetations. The antibiotic chosen should bactericidal and has to be given for a prolonged period of time (6-8weeks). The mode of administration should be intravenous whenever possible. The dose given should be modified ideally on the basis of the results of the serum bactericidal levels. Optimal therapy depends on isolating the infective organism and determining its drug susceptibility. In toxic patients, therapy should be initiated immediately while in less toxic patients, treatment may be delayed until blood culture results are known.

Since Streptococcus viridans continue to be the most common cause of endocarditis, penicillin remains an antibiotic of choice to initiate therapy.

Penicillin alone is sufficient when the organism is sensitive to serum levels of penicillin of 0.1 mcg/ml or less. If organisms require more than 0.1 mcg/ml penicillin as it occurs in 10% of the patients, larger doses of penicillin are used or an aminoglycoside is added. The synergism between penicillin and aminoglycoside has been demonstrated. When penicillin is contraindicated cephalosporin or vancomycin is indicated.

Treatment for enterococci requires the use of ampicillin or penicillin and aminoglycoside.

For, methicillin-sensitive staphylococcal aureus - Nafcillin or cefazolin with aminoglycoside and for methicillin-resistant staphylococci- vancomycin and aminoglycoside or vancomycin and rifampicin with aminoglycoside give better results.

Amphotericin B is the drug of choice in endocarditis due to candida and therapy should continue for 6 weeks.

If treatment is initiated before blood cultures are obtained or in culture-negative endocarditis, a combination of penicillin and aminoglycoside can be used. If there will be no improvement within 72 hours, vancomycin should replace penicillin. In postoperative endocarditis, therapy should be initiated using vancomycin.

If blood cultures continue to be negative for 2 weeks after the onset of therapy, the patient has to be reevaluated. If there is clinical improvement therapy should be continued and if there is no improvement, attempts at identifying fastidious organisms and fungi should be made and proper therapy instituted.

Despite aggressive medical therapy of infective endocarditis and its complications, some patients may prove refractory to treatment. In these patients, surgical intervention may prove not only necessary but life-saving.

Prognosis

Survival of patients with infective endocarditis depends upon the causative organism and associated complications. The mortality rate is 7-10% with streptococcus viridans and 25% with staphylococcus aureus. It is more in infants and in patients without co-existing heart disease and fungal IE. Most deaths are due to complications of embolic episodes and refractory heart failures. Few patients die due to sepsis.