Jane W. Newburger
Infective endocarditis (IE) is defined as an infection of the endocardium, generally involving cardiac valves and their valvular apparatus such as the chordae tendinae, interventricular septum, mural endocardium, or intracardiac devices. IE may occur in children with or without antecedent underlying cardiac disease. The diagnosis of IE rests on a constellation of clinical features and laboratory investigations, including blood cultures and echocardiography.1Most often, IE presents with fever, positive blood cultures, a new murmur, or vegetations by echocardiography. Vascular findings and immunologic phenomena are common. The presenting symptoms, rate of progression, morbidity, and mortality of infective endocarditis depend, in part, upon the underlying heart disease, the etiologic organism, and host factors. Whereas most infective endocarditis is accompanied by positive blood cultures, 5% to 7% are culture negative, sometimes due to administration of antibiotics before blood cultures were obtained.1 Compared to adults, children have a lower incidence and fatality rate of IE.2,3 The most common causes of bacterial endocarditis in children are viridans group streptococci and Staphylococcus aureus; other principal pathogenic agents include coagulase-negative staphylococci, Streptococcus pneumoniae, HACEK organisms (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species), and enterococcus species.4-6 Emergence of antibiotic resistance to these common pathogens has serious ramifications for the morbidity and mortality of IE. It is therefore essential that pediatricians and pediatric cardiologists work in concert with specialists in infectious diseases in planning the treatment of IE.
CLINICAL FEATURES AND DIFFERENTIAL DIAGNOSIS
Infective endocarditis (IE) is readily diagnosable in children with at least 2 positive blood cultures, structural heart disease, and vegetations as identified by echocardiography. However, the diagnosis can be challenging, for example, when a patient with structural heart disease has bacteremia. To aid diagnosis and facilitate epidemiologic and clinical research efforts, the modified Duke criteria have become the gold standard for diagnosis of infective endocarditis. These criteria classify endocarditis as definite, possible, or rejected, based upon particular pathologic findings or combinations of major and minor clinical criteria.13 (See Table 490-1.)
A typical history for the patient with subacute IE includes nonspecific symptoms, such as low-grade fever, malaise, fatigue, weight loss, headache, arthralgias, and myalgias. Presentation may also be fulminant, with acute symptoms and high fever. Careful daily physical examination reflects changes in cardiac structure or function, as well as embolic, vascular, or immune phenomena. Specifically, IE may cause new or changing heart murmurs, and worsening valvular regurgitation may cause congestive heart failure. Occlusion of a systemic to pulmonary artery shunt in a child with cyanotic heart disease may decrease oxygen saturation. Septic emboli may cause ischemia or hemorrhage in, for example, the kidneys, spleen, or brain. Patients with right-sided endocarditis may have septic pulmonary emboli. Mycotic aneurysms in the central nervous system or viscera are at risk for rupture. Vascular and immune phenomena include petechiae, most commonly present on the extremities, oral mucosa (eg, palate), or conjunctivae, best seen on eversion of the upper and lower eyelids. Splinter hemorrhages are nonblanching lines of maroon color under the proximal nail beds. Roth spots are retinal hemorrhages with white or pale centers composed of coagulated fibrin caused by immune complex deposition. Janeway lesions are painless hemorrhagic cutaneous lesions on the palms or soles due to a microabscess of the dermis formed by deposition of circulating immune complexes in small blood vessels. Osler nodes are painful subcutaneous lesions on the distal fingers caused by immune complex deposition. Glomerulonephritis and splenomegaly may also be caused by immune phenomena.
Table 490-1. Revised Duke Clinical Diagnostic Criteria for Infective Endocarditis
|
For definite clinical diagnosis: 2 major criteria or 1 major and 3 minor criteria or 5 minor criteria. |
|
For possible clinical diagnosis: 1 major criterion and 1 minor criterion or 3 minor criteria. |
|
For rejection of diagnosis: Firm alternative diagnosis explaining the findings of infective endocarditis, resolution of symptoms and signs after antimicrobial therapy for ≤ 4 days, no pathologic evidence of infective endocarditis found during surgery or autopsy, or failure to meet the clinical criteria for possible endocarditis. |
|
Major Criteria |
|
Two positive blood cultures for organisms typical of endocarditis |
|
Three positive blood cultures for organisms consistent with endocarditis |
|
Serologic evidence of Coxiella burnetii |
|
Echocardiographic evidence of endocardial involvement: |
|
Oscillating intracardiac mass on a heart valve, on supporting structures, in the path of regurgitant jets, or on implanted material without another anatomic explanation |
|
Cardiac abscess |
|
New dehiscence of prosthetic valve |
|
New valvular regurgitation |
|
Minor Criteria |
|
Predisposing heart disorder |
|
IV drug abuse |
|
Fever ≥ 38° C |
|
Vascular phenomena: |
|
Arterial embolism |
|
Septic pulmonary embolism |
|
Mycotic aneurysm |
|
Intracranial hemorrhage |
|
Conjunctival petechiae |
|
Janeway lesions |
|
Immunologic phenomena: |
|
Glomerulonephritis |
|
Osler’s nodes |
|
Roth’s spots |
|
Rheumatoid factor |
|
Microbiologic evidence of infection consistent with but not meeting major criteria |
|
Serologic evidence of infection with organisms consistent with endocarditis |
DIAGNOSTIC EVALUATION
At least 3 blood cultures, from separate veni-puncture sites, should be obtained prior to instituting antibiotic therapy when infective endocarditis (IE) is suspected.17 Because bacteremia is constant in IE, the cultures can be obtained at any time, regardless of fever spikes or shaking chills. When presentation of IE is indolent, blood cultures can be obtained over the course of a day or two. In contrast, the child with acute presentation, in whom initiation of empiric antibiotic therapy is urgent, undergoes serial blood cultures in rapid succession, for example, over the course of an hour. In patients with subacute presentation with previous antibiotic treatment, up to 6 blood cultures may be useful. The yield from blood cultures is related to the amount of blood inoculated.18 At least 5 cc per blood culture is optimal in children (in young infants, as little as 0.5 cc may be inoculated). In the larger child or adolescent, a minimum of 10 cc is ideal. In patients with suspected culture-negative endocarditis, serologies and molecular techniques such as polymerase chain reaction may help.1
Two-dimensional echocardiography can detect vegetations, myocardial abscesses, and valvular insufficiency. Although transthoracic echocardiography is more sensitive in young children than in adults, transesophageal echocardiography is more likely to identify vegetations in the child or adolescent with poor echo windows, for example, in the obese or muscular larger child or adolescent or for those after recent cardiac surgery or who have respiratory symptoms with pulmonary hyperinflation.2
Electrocardiography should be performed daily in patients with aortic valve endocarditis to monitor conduction system disturbances.
TREATMENT
Intravenous antibiotics are the standard of care for definite or probable infective endocarditis.1,2 The choice of antibiotics, duration of therapy, and need for surgical intervention are determined by the specific etiologic pathogen and the site of infection (eg, native valve, prosthetic valve). Wherever possible, antibiotics should be bactericidal rather than bacteriostatic and administered intravenously. The duration of therapy is usually 4 to 8 weeks. Multiple antibiotics should be administered at approximately the same time to maximize synergism. Blood cultures should be performed daily until bacteremia has resolved for 48 hours. Absolute indications for surgical intervention include: congestive heart failure; valve obstruction, a definitive perivalvular abscess, non-candidal fungal infection; and left-sided infective endocarditis caused by gram-negative bacteria, especially pseudomonas. Relative indications include persistent bacteremia after 1 week of antibiotics; candidal endocarditis or vegetations of size greater than 10 mm. Surgical therapy is more frequently required for prosthetic valve infective endocarditis than native valve infective endocarditis.
PROGNOSIS OR OUTCOMES
Most patients with infective endocarditis are cured with antibiotic therapy and, occasionally, surgical management. Patients should receive an echocardiogram after treatment ends to establish a new baseline. In afebrile and asymptomatic patients, blood cultures should be repeated twice within 8 weeks after completing the antibiotic course. Because endocarditis may relapse, families should be educated to report the occurrence of fever or systemic signs and symptoms promptly. Empiric treatment with antibiotics for fever should be discouraged. Patients should also be monitored for developing or worsening congestive heart failure. Those treated with aminoglycosides should have audiograms. Because prolonged antibiotic use may be associated with delayed Clostridium difficile colitis, patients should report the occurrence of diarrhea promptly. Finally, patients who have had one episode of infective endocarditis are at much higher risk for repeated episodes, so physicians should have a low threshold for repeat blood cultures and avoidance of unnecessary antibiotics.
PREVENTION
The most recent American Heart Association recommendations advise use of antibiotic prophylaxis prior to dental procedures only in patients who are at highest risk for morbidity and mortality if they develop infective endocarditis.9 This includes patients with: 1) prosthetic cardiac valves or prosthetic material used for cardiac valve repair; 2) previous infective endocarditis; 3) unrepaired cyanotic congenital heart disease, including palliative shunts and conduits; 4) completely repaired congenital heart defects with prosthetic materials or devices placed either by surgery or by catheter intervention during the first 6 months after the procedure; 5) repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device: and 6) cardiac transplantation recipients who develop cardiac valvulopathy. Amoxicillin is the preferred antibiotic for prophylaxis. For patients allergic to penicillin or amoxicillin, cephalexin or another first-generation oral cephalosporin, clindamycin, azithromycin, or clarithromycin is recommended. Prophylaxis is also recommended in these patients with invasive procedures involving incision or biopsy of respiratory tract mucosa, procedures on infected skin or muscle tissue, but not for routine genitourinary or gastrointestinal tract procedures.
When patients are already taking an antibiotic that is recommended for infective endocarditis dental prophylaxis, an antibiotic from a different class should be selected because of the growth of resistant organisms in the oral cavity. If possible, it is best to delay a dental procedure until at least 10 days after completion of the antibiotic therapy. This might allow time for the usual oral flora to be reestablished.