Microbiology The majority of both native and prosthetic valve IE is caused by gram-positive bacteria The likely reason for this is the specific capacity of these organisms to bind to surface-exposed host receptors in denuded injured subendothelial matrix Work has further elucidated the complex mechanisms and interrelationships between bacterial binding and the formation of biofilm on host subendothelial surfaces Streptococci and Enterococci Species One of the best-characterized bacteria that cause IE is the viridans streptococcus, Streptococcus gordonii.80 The multifunctional fibrillar adhesin CshA81 can promote binding of bacteria to host cell matrix by forming molecular bridge to host cell integrin in the subendothelial matrix.82 Initial binding of S gordonii to two cell surface proteins, Hsa and platelet adherence protein A, mediates adherence and activation of platelets, mediating binding to subendothelial matrix proteins vitronectin and fibronectin, promoting biofilm formation.83 In Enterococci spp., common causative pathogens in adults, it has been shown that the gene product of bepA, a carbohydrate phosphotransferase system permease, is linked to metabolism of glycosaminoglycan-injured heart valves.84 Staphylococcus Aureus and Other Staphylococci S aureus expresses cell wall–anchored (CWA) proteins The most common group of these are the microbial surface components recognizing adhesive matrix molecules.85 These are multifunctional receptors (such as clumping factor A, fibronectin-binding proteins) involved in adhesion to subendothelial matrix proteins such as fibronectin but are also involved in tissue invasion, immune deviation, and establishment of biofilm formation.86 S aureus expresses up to 24 different CWA proteins, whereas coagulase-negative strains often express a smaller number of these proteins It is very likely that the increased virulence of S aureus is likely to involve the plethora of CWA proteins it is able to utilize in host cell and matrix interactions sarA, a global regulator of many S aureus virulence factors, may be intricately involved in both regulation of biofilm production but also resistance to oxacillin, via its regulation of penicillin-binding protein 2b in methicillin-resistant strains, because sarA-deficient mutants produced significantly less biofilm and were more susceptible to oxacillinmediated killing in experimental endocarditis models.87,88 These investigations provide further rationale to develop novel interventions, such as vaccines designed to elicit antibodies that block microbial host cell interactions or compounds designed to interrupt microbial regulatory mechanisms Vaccine strategies to induce protective antibodies in S aureus89 and Enterococcus faecalis90 have been shown to be effective in experimental endocarditis In animal models, vaccination strategies to induce antibody to Hsa and platelet adherence protein A protected against experimental endocarditis.91 In the longer term, such strategies could be more effective than antimicrobial prophylaxis, especially in high cases Infective Endocarditis Causative Agents: Drivers for Changing Epidemiology ■ As the underlying risk factors for IE have changed over the past 4 decades, there have been changes in the proportion of the microbial agents responsible ■ There has been a reduction in rheumatic heart disease in developed countries in particular, with a concomitant rise in survival, and surgical intervention and management of children with CHD ■ Heath care interventions and increasing survival of preterm neonates and other children requiring longterm central venous access (such as treatment of malignancy) has increased risk factors for IE in the absence of CHD ■ In adults, large-scale epidemiologic studies have demonstrated a significant increase in staphylococcal spp., both S aureus and so-called coagulase-negative staphylococci (CONS), in keeping with changing risk factors over the past 3 to 4 decades.92 ■ Relatively few studies have looked at the incidence and changes in risk factors and causative agents in children There has been a similar trend in increase in staphylococcal IE in the past few decades However, one factor that may have driven this in adults, namely intravenous drug abuse,92 is very uncommon in children Comments on the causative agents in pediatric IE and studies on these are summarized in Tables 56.4 and 56.5 Table 56.4 Causative Agents and Comments Causative Agent(s) Notes and Comments Staphylococcus aureus Predominant and one of the most virulent causes of IE Associated with tissue destruction and root abscesses More common in absence of CHD Highest mortality rates, especially in neonates CoagulaseMore likely to affect indwelling cardiac implants such as shunts and artificial valves negative Often associated with indwelling central venous lines, though can be implanted at staphylococci: surgery S epidermidis (most Can cause NVE, but very rare in children compared with adults ... one factor that may have driven this in adults, namely intravenous drug abuse,92 is very uncommon in children Comments on the causative agents in pediatric IE and studies on these are summarized in Tables 56.4 and 56.5 Table 56.4 Causative Agents and Comments