Although infective endocarditis is a relatively uncommon diagnosis in children, it is an important cause of morbidity and mortality in the pediatric population.¹ The incidence of this disease appears to be increasing in patients with known cardiac disease and in other groups as well.^2,3 For these reasons, the pediatric hospitalist must be well versed in the epidemiology, causative factors, and treatment of this disorder.

Over the past several decades, altered rates of predisposing risk factors have driven changes in the epidemiology of infective endocarditis. For instance, the decline in rheumatic heart disease has meant a corresponding decline in infective endocarditis resulting from this illness. Conversely, in the United States and other developed nations, an increase in infective endocarditis has occurred among children with congenital heart disease. This includes not only children with untreated cardiac conditions, such as small ventricular septal defects, but also children who have had corrective or palliative surgery, including implanted grafts or patches, prosthetic valves, and conduits. A review of the modern epidemiology of infective endocarditis after surgery for congenital heart disease found that the highest annualized risk was in patients who had had interventions for cyanotic forms of congenital heart disease, including relief of obstructed pulmonary blood flow.³ Among the acyanotic group, a higher incidence of infective endocarditis occurred in patients who had prosthetic aortic valve placement.

In addition to the rising prevalence of infective endocarditis among survivors of congenital heart disease, the same trend is occurring in certain children without structural heart disease. As many as 8% to 10% of children with infective endocarditis have no known primary cardiovascular abnormality.⁴ This group includes children with chronic indwelling central venous catheters, newborns (particularly premature babies, who are increasingly subjected to invasive procedures), and adolescent intravenous drug abusers.

Studies of animal models confirm that the development of a nidus for endocardial infection requires a locus of denuded endothelium as well as exposure to bacteria.⁵ The disrupted endothelial surface exposes collagen to the bloodstream, which leads to the deposition of fibrin and platelets and the formation of a thrombotic vegetation. Circulating microorganisms, most commonly bacteria, can become embedded in the vegetation, resulting in an endocardial infection. Additional deposits of platelets and fibrin form protective layers that shield the pathogens from host immune defenses. As the process continues, the vegetation grows, creating layers of embedded microorganisms. The organisms sequestered within the vegetation have a great potential for proliferation.

Congenital heart lesions with high-velocity blood flow jets are most susceptible to vegetation development, owing to the potential for endothelial damage. Adding appreciably to this risk is the presence of foreign material, which itself can offer a site prone to the development of platelet and fibrin plugs. Patients with surgically placed grafts or palliative shunts (e.g. Blalock-Taussig shunts) are thus at high risk for infective endocarditis.⁶

In addition to host factors, a better understanding of virulence factors associated with the organisms themselves has contributed to insight into the pathogenesis of infective endocarditis. Such factors include the ability to produce adhesins that facilitate binding of bacteria, to generate biofilms that cover devices such as prosthetic valves, and to stimulate platelet aggregation, which enhances the propagation of vegetations.⁷

Gram-positive cocci remain the largest single group of organisms associated with infective endocarditis in children. Table 54-1 outlines common causative organisms. After the first year of life, viridans streptococci predominate (including S. sanguis and S. mitis), with Staphylococcus aureus ranking second. S. aureus remains the most common cause of endocarditis occurring acutely and is the most common agent in children without structural heart disease. Coagulase-negative staphylococci are also causative agents in these children, especially those with chronic indwelling catheters. Gram-positive cocci are often associated with infective endocarditis in newborns.⁷ Less common organisms include enterococci and fungi. Interestingly, children with congenital or acquired immunodeficiency states are not at increased risk for infective endocarditis unless other risk factors are present.

The immunologic sequelae of infective carditis are not well understood. The infection results in extensive activation of both the cell-mediated and the humoral immune systems. Especially with long-standing disease, patients are often found to be hypergammaglobulinemic (also represented by elevated rheumatoid factor levels) and to have elevated levels of circulating immune complexes. These immune complexes are thought to play a role in renal disease and may also be involved in some of the secondary symptoms and complications that occasionally arise (e.g. Osler nodes and glomerular nephritis).

The presentation of infective endocarditis may be indolent (subacute) or fulminant (acute). The clinical picture relates to the combination of systemic responses to bacteremia or fungemia, the local mechanical impact of the vegetation, and in some cases, the deleterious effects of embolic and systemic immunologic responses.

Classically, in subacute bacterial endocarditis, somatic complaints predominate. These nonspecific symptoms include low-grade fever, malaise with weakness and fatigue, anorexia (often with weight loss), intermittent diaphoresis, myalgias, and arthralgias. This group of complaints should raise the suspicion for subacute bacterial endocarditis, especially in the context of a child at risk for infective endocarditis.

In addition to these general complaints, focal signs should be sought. Cardiac manifestations result from either direct valve damage or valvulitis. Thus new murmurs may appear, such as mitral or aortic regurgitation, and symptoms of congestive heart failure may develop or worsen.

Extracardiac manifestations can also be helpful in establishing the diagnosis, although they occur less frequently in children than in adults. Skin findings such as petechiae, splinter hemorrhages in the nail beds, Janeway lesions (nontender hemorrhagic plaques on the palms and soles), and Osler nodes (tender purplish lesions on the pads of fingers and toes, thenar eminences, and lower arms) may be found on examination. Janeway lesions are thought to represent septic emboli; however, it is unclear whether Osler nodes are attributable to the same phenomenon or are due to an immune vasculitis. Roth spots are pale retinal lesions with areas of hemorrhage usually located near the optic disk. Emboli to any organs, including the heart, kidneys, lungs, brain, spleen, or liver, can cause infarction (thrombotic emboli) or abscess (septic emboli). Emboli to the central nervous system can result in stroke or mycotic aneurysm. Mycotic aneurysms develop when septic emboli cause local arterial infection and inflammation with resulting occlusion of the vessel. The damage to the muscular wall and increased pressure cause dilation of the vessel. Despite the name, these aneurysms almost always result from bacterial infection. Splenomegaly is seen in more than half of patients and can be caused by immune system activation. Both focal and diffuse glomerular nephritis have been described, with immune complex deposition noted.

Patients with rapidly progressing acute endocarditis may present in shock, with a clinical picture consistent with overwhelming sepsis. In such circumstances, the classic findings of infective endocarditis may be absent, and suspicion for this disease may be raised only by a history of cardiac lesions and persistently positive blood cultures.

Alternative diagnostic considerations are extremely broad and are based on the predominant signs and symptoms. Prolonged fever should prompt evaluation for a fever of unknown origin. Neurologic features may suggest a wide range of intracranial conditions, including stroke, epilepsy, and encephalopathy. Rheumatologic and oncologic processes can mimic the nonspecific findings of fatigue, malaise, weight loss, and joint pain.

The diagnosis of infective endocarditis can be elusive and hinges on a careful assessment of risk factors in the setting of suggestive findings. In an attempt to improve the clinical diagnosis of infective endocarditis, Durack and colleagues developed a scoring system.⁹ This was subsequently modified to include a greater emphasis on imaging data.¹⁰ These diagnostic criteria have been tested in pediatric populations and found to be useful.^4,10,11 Tables 54-2, 54-2, 54-3 outline the definitions of and criteria for the diagnosis of infective endocarditis.

IMAGING

Echocardiography with Doppler color flow mapping is the standard diagnostic modality in patients with suspected infective endocarditis. It can identify valvular vegetations (Figure 54-1) as well as impaired cardiac performance, prosthetic valve dehiscence, disturbed conduit flow, and abscess. Moreover, echocardiography can define the presence of an occult structural abnormality, such as a bicuspid aortic valve, thus identifying a clinically silent risk factor. It has been well established that echocardiography can detect cardiac involvement in patients with otherwise occult infective endocarditis,¹² and this has been confirmed in children.¹³