This knowledge serves as a foundation for the development of novel clinical tools that include therapeu- tics and vaccines. Indeed, identification of a virulence factor resulted in development of a vaccine that reduced the risk of endocarditis development in an animal model.33 Pathogenesis of IE on Prosthetic Material Because perivalvular infection that involves the sewing ring is commonplace among patients with prosthetic valve endocardi- tis, particularly mechanical valves, the pathogenic mechanisms reviewed previously in this section apply to prosthetic valve endocarditis. In addition, biofilm formation can be operative in infection of prosthetic valves, similar to infection of a broad array of indwelling cardiovascular and noncardiovascular devices.34 A mature biofilm represents a unique and complex environ- ment for organisms to attach to and thrive on a device surface. Both antimicrobial agents and immune cells have difficulty in penetrating biofilm, and because of metabolic changes of infecting organisms in biofilm, the ability of antimicrobial agents to kill biofilm-associated organisms is greatly reduced. Because of this, infection relapse at a prosthetic valve site is thought to be increased. Oral/Dental Considerations The oral mucosa and tooth surfaces of children who are beyond infancy are populated by a variety of pathogenic and Baltimore et al Infective Endocarditis in Childhood: 2015 Update 1491 nonpathogenic bacteria, which are representative of hun- dreds of strains of aerobic and anaerobic species.,35,36 This oral flora, in both health and disease, is different from adults and less diverse, but it becomes more like that of adults as the child ages, including increases in the percentage of VGS ( -hemolytic streptococci), Prevotella, and Actinomyces spe- In health, the child s oral flora has a variety of VGS, Neisseria species, Haemophilus species, and Staphylococcus species. 