Infective Endocarditis in Children: Still Much to Learn in an Increasingly Frequent Disease

It has been 13 years since the American Heart Association (AHA) published a comprehensive guiding document on infective endocarditis (IE) in childhood. Importantly, now the AHA has assembled an expert multidisciplinary writing group to readdress the topic, taking into consideration the changing epidemiology of pediatric IE and over a decade of research into its pathogenesis, diagnosis, and treatment. The AHA scientific statement “Infective Endocarditis in Childhood: 2015 Update” specifically addresses the controversial subject of antibiotic prophylaxis for IE prevention and gives updated recommendations on the appropriate use of outpatient therapy for children with clinically stable IE.

The epidemiology of pediatric IE in high-resource nations has shifted dramatically in the past 50 years. While in most low- and middle-income countries, rheumatic heart disease (RHD) remains the most common underlying substrate for development of IE,¹ RHD has largely disappeared from pediatric populations in high-income countries. However, instead of IE following the decline in RHD prevalence, pediatric IE may be on the rise.² This has been attributed both to improved survival among children with congenital heart disease (CHD) and to the increase in the number of premature and medically complex neonates being managed with long-term intravenous support.³

Echocardiography has improved substantially over the last decade. While transesophogeal echocardiography (TEE) remains the gold-standard for diagnosis of IE in adults, transthoracic echocardiography (TTE) has been shown to have 97% sensitivity for detection of endocarditis in young children, in particular those less than 10 years of age and 60 kg.⁴ The writing group now recommends TEE in this group only when high-risk feature are present –chest wall disruptions (Class I, Level of Evidence B) and/or suspicion of aortic root abscesses (Class IIa, Level of Evidence C).

Since the last iteration, there has been a shift away from antibiotic prophylaxis prior to dental procedures and an emphasis on encouraging overall oral hygiene, which is reinforced by the writing group (Class IIa, Level of Evidence B). This is largely due to studies that suggest bacteremia resulting from daily oral activities creates a more frequent and greater annual bacterial load than intermittent dental office procedures.⁵ In 2007, the AHA published recommendations that advised IE prophylaxis was only needed in the highest risk patients.⁶ In 2008, the National Institute for Health and Clinical Excellence (United Kingdom) went a step further, concluding that antibiotic prophylaxis for IE was no longer indicated for any patient.⁷ Since these recommendations have been in place, there has been limited but conflicting data on changing IE incidence. Importantly, these data come from high-income countries, and should not be generalized to areas where RHD remains endemic. Epidemiological surveys pre- and post-guideline changes in children in England⁸ and adults in France⁹ reported no increase in overall IE prevalence, and the latter also specifically reported no increase in oral streptococcal IE. Conversely, in an adult US population, no increase in overall IE was found, but there has been a significant increase in oral streptococcal IE.¹⁰ Based on the best available evidence, the writing group stands with the 2007 AHA recommendations (Class IIb, Level of Evidence C), but longer-term data, including high-quality pediatric studies, are needed to definitively determine the impact of reduced IE prophylaxis in children with congenital heart disease.

The typical duration of treatment for IE ranges from 4-6 weeks, and many stable children with IE now complete their treatment at home. Change from intravenous to oral therapy is not recommended, and home therapy can increase patient comfort and potentially reduce healthcare expenditures. The writing group emphasizes that the decision regarding home IV therapy should be highly individualized, and based on symptomatic recovery during initial treatment, cardiac stability, and the ability of the family to follow the prescribed treatment and have rapid access to a healthcare facility if needed (Class IIb, Level of Evidence C). Importance is placed on considering factors that put children at high risk for complications and in making the decision regarding home-therapy with input from a multidisciplinary team. While previous publications have identified mainly stable patients with streptococcal IE as candidates for home-based treatment, there are no infectious etiologies of IE specifically excluded for the consideration of home IV therapy (including staphylococcal IE) in the current recommendations.

The importance of a multidisciplinary team including early consultation with specialists in pediatric infectious disease (ID) is also highlighted throughout this statement. Adult data show that care by a multidisciplinary team including cardiologists, ID specialists, and cardiac surgeons improves outcomes.¹¹ While no specific data exist for children, it stands to reason that this type of collaborative care would also improve pediatric IE outcomes. Additionally, the authors recommend that all patients with IE benefit from pediatric ID consultation, but specifically recommend early consultation with the ID team and/or the microbiology laboratory for patients in whom fastidious organisms are suspected, who have already received antibiotics, who have culture-negative endocarditis, and who have non-penicillin susceptible S. pnemoniae IE, enterococcal IE, S. aureus IE, or fungal IE (for the latter two rapid access to cardiac surgery should also be available).

It is important to point out that the majority of recommendations in this statement remain extrapolated from adult data or are based on expert opinion. In fact, only 2 specific recommendations were assigned a Level of Evidence A – or based on randomized controlled trials (one extrapolated entirely from adult data). The scarcity of research in pediatric IE is in part responsible for the lack of evidence-based guidelines in respect to cardiac surgery and its timing (emergency, urgent, or elective). Specific recommendations in the timing of cardiac surgery were updated in 2014 for adults¹² but cannot necessarily be translated to the pediatric population. Unlike in adults, prophylactic surgery to prevent a primary embolic event is not recommended in children (Class III, Level of Evidence C).

In conclusion, the authors of “Infective Endocarditis in Childhood: 2015 Update” should be applauded for taking on an extremely ambitious, comprehensive update to IE in children. We have attempted here to highlight the most important advances compared to the 2002 version, but recommend a complete read for all practitioners who care for children with or at-risk for IE. While it is unlikely that pediatric randomized control trials in IE will ever be feasible (given large amounts of adult data and relative rarity of IE in children) multi-institutional, perhaps even multinational collaborative networks, should be prioritized in order to build our pediatric-specific knowledge regarding IE epidemiology, diagnosis, and treatment.