It has been estimated that fewer than one-third of cases of neonatal endocarditis occur in the presence of congenital cardiac disease.24 26 A recent review showed that 31% of infants who died of IE were premature.24 The most common infecting organisms were S aureus, coagu- lase-negative staphylococcus strains, Gram-negative bacterial species, and Candida species. The clinical manifestations of IE in the neonate are vari- able and nonspecific and may be indistinguishable from sep- ticemia or from congestive heart failure associated with other In infants, septic emboli from IE are common, resulting in foci of infection outside the heart (eg, osteomy- elitis, meningitis, or pneumonia). Neonates with IE often have feeding difficulties, respiratory distress, tachycardia, and hypotension. As with older children, neonates also may have a new or changing heart murmur. Many neonates with IE also have neurological signs and symptoms (eg, seizures, hemipa- resis, or apnea). However, although arthritis and arthralgia are common findings in older children with IE, arthritis is rarely described in neonates. Osler nodes, Roth s spots, Janeway lesions, and splinter hemorrhages are also not mentioned in published cases of IE in neonates. Pathogenesis Early histopathologic studies in humans and decades-long investigations that have included an animal model of experi- mental endocarditis have confirmed 2 critical histopathologic findings: (1) Damaged or denuded endothelium is necessary for initial pathogen colonization of a cardiac nidus; and (2) Gram-positive cocci, the predominant pathogens in both native and prosthetic value infections, express multiple adhesins that serve as virulence factors through their ability to enhance host cell/substrate attachments that are important in both the initia- tion and propagation of endocardial infection. (Adhesins are discussed further in a separate section.) 