Pediatric infective endocarditis (IE) is a diagnostically challenging infection in children, as it often presents with vague or subtle signs and symptoms. When suspected, significant hospital resources and subspecialty support are needed. While the incidence is rare, if missed, the disease is associated with significant morbidity and mortality. It is therefore imperative that emergency physicians understand the unique features of IE in the pediatric population, as well as the appropriate diagnostic tools and most current treatment recommendations.
Epidemiology
In general, IE occurs less often in children than it does in adults. Surprisingly, the incidence of pediatric IE has actually increased in recent years, largely due to improved survival among children with congenital heart disease (CHD) in developed countries, despite the significant decrease in rheumatic heart disease.1 Studies have estimated that anywhere between 50% and 90% of pediatric patients with endocarditis had a prior history of CHD and/or cardiac repair.2,3,4
In addition, the more complex management of patients in neonatal and pediatric intensive care units have increased the amount of pediatric patients who develop catheter-related IE, with or without underlying CHD.1 Immunocompromised states with co-existing oncologic, immunologic, or infectious disease processes place older children at risk, while lifestyle factors such as intravenous drug abuse play an increasing role in adolescent populations.5
Pathophysiology
Infectious endocarditis occurs when damaged endothelium or valvular tissue produces an environment where platelets and fibrin deposit, thus providing a nidus in which organisms can adhere and form an infected vegetation.1
As with adults, gram-positive bacteria represent the majority of organisms responsible for pediatric IE. This includes viridans group streptococci, staphylococci (most dangerously methicillin-resistant S. aureus), and enteroccoci.
Less frequently, gram-negative species such as the HACEK group (Hemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella species) are implicated in the pathogenesis of IE. Fungal endocarditis is usually caused by Candida and less likely Aspergillus species.6-7
Culture-negative IE can occur in up to 5% to 10% of children. This diagnosis is made when a patient has clinical evidence of IE but persistently negative blood cultures.1 It occurs more frequently when HACEK and fungal organisms are the causative etiology, as they are difficult to grow on a standard culture medium. It may also occur in the setting of previous antibiotic use, or when the organisms remain walled-off within a vegetation.7
Diagnosis
The presentation of endocarditis can be categorized into fulminant (acute) and subacute processes. These classifications refer to both rate and severity of disease progression. Fulminant endocarditis, for example, can occur over days to weeks, and is often compounded by distributive and cardiogenic shock. Rapid assessment, stabilization, and intensive therapy are indicated immediately.
Most cases of pediatric endocarditis, however, present subacutely. Signs and symptoms are often vague and nonspecific, and include low-grade fever, malaise, myalgias, arthralgias, and headaches.6,7 On exam, a new or changing heart murmur may be auscultated. Of course, a history of CHD, prior cardiac surgery, prior indwelling catheter, prosthetic material and/or prior valvular damage should increase suspicion.
Several studies have verified that the Duke criteria remain superior to other criteria for the diagnosis of IE in children. As a reminder, these criteria utilize clinical, microbiologic, and echocardiographic components and require a combination of major and/or minor criteria in order to make the diagnosis. Important differences include the fact that extracardiac manifestations of IE (eg, Janeway lesions, Osler's nodes) are less common in children than adults. Typically, the recommendation is for 3 blood cultures to be drawn at least an hour apart on the first day, followed by 2 more on the second day if there is no growth.1
Endocarditis remains a difficult diagnosis to make, particularly in the emergency department. Limited diagnostic criteria at time of presentation and absence of echocardiographic evidence contribute to the diagnostic dilemma. In addition, laboratory evaluation in the emergency department is often inconclusive and nonspecific.1,5,7 As a result, many patients are initially misdiagnosed before being correctly identified on a return visit.8 There is value in point-of-care ultrasound, which may expedite diagnosis and treatment. The comfort and skill level of the ultrasonographer and the identification of a vegetation or new valvular damage are all factors that contribute to early and accurate diagnosis.9
Treatment and Complications
In general, the principles of management of pediatric IE are similar to those for treatment of adult IE. If and when endocarditis is suspected, a multidisciplinary approach is necessary. Support from cardiology, infectious disease, and intensive care may be required. Empiric antibiotics should be initiated after cultures are obtained. As cultures speciate, a transition to sensitivity-based targeted therapy will be appropriate. Antibiotics are typically continued for 4-6 weeks.
Factors that predispose to the development of complications include type of organism, location and size of vegetation, and presence of other comorbid medical conditions, particularly cardiac issues. Intractable heart failure, uncontrolled infection, prosthetic valve or shunt endocarditis, and embolic events may require surgical intervention.6 Furthermore, severe neurological manifestations may occur with bacterial dissemination to the brain. Because of these types of complications, endocarditis carries a significant mortality rate of 6-14%.2,5,7
Conclusion
Pediatric IE is a rare but dangerous condition whose diagnosis requires a high level of suspicion. Since it often presents subacutely and in a child with undifferentiated fever, one must be sure to inquire about prior history of CHD, cardiac surgery, or history of indwelling catheter in a previously critically ill child. While the diagnosis is not always made in the emergency department, appropriate level of concern is the key to preventing morbidity and mortality.
References
- Ferrieri P, Gewitz MH, Gerber MA et al. Unique features of infective endocarditis in childhood. Pediatrics. 109(5):931-943. 2002.
- Day MD, Gauvreau K, Shulman S et al: Characteristics of children hospitalized with infective endocarditis. Circulation. 119:865-870. 2009.
- Martin JM, Neches WH, Wald ER. Infective endocarditis: 35 years of experience at a children's hospital. Clin Infect Dis. 24:669–675. 1997.
- Tseng W, Chiu S, Shao P et al: Changing spectrum of infective endocarditis in children: A 30 years experiences from a tertiary care center in Taiwan. Pediatr Infect Dis J. 33: 467-71. 2014.
- Tsai WT. “Inflammatory and Infectious Heart Disease.” In Strange and Scahfermeyer's Pediatric Emergency Medicine, 4th Edition. p274-277. McGraw Hill. New York. 2015.
- Bragg L, Alvarez A. Endocarditis. Pediatrics in Review. 2014;35(4):162-167.
- Hoyer A and Silberbac M: Infective endocarditis. Pediatrics in Review 26(11): 394-400. 2005.
- Lewena, S. Infective endocarditis: Experience of a paediatric emergency department. J Paediatr Child Health. 41:269-272. 2005.
- Cheng AB, Levine DA, Tsung JW, Phoon CK. Emergency physician diagnosis of pediatric infective endocarditis by point-of-care echocardiography. Am J Emerg Med. 2012;30(2): 386e1-386e3.