Early surgical correction of lesions that were major risk factors for IE in the past has also changed the substrate for this disease. Although congenital heart defects, such as aortic valve abnormalities, ventricular septal defect, and tetralogy of Fallot, are still common under- lying conditions, an increasing proportion of children with IE have had previous corrective or palliative surgery for complex cyanotic CHD, with or without implanted vascular grafts, patches, or prosthetic cardiac valves.10 14 Postoperative IE is a long-term risk after correction of complex CHD, especially in those with residual defects or in cases in which a surgical shunt is constructed or other prosthetic material is left in place. Increasingly, IE develops in the absence of CHD. This cir- cumstance is often associated with central indwelling venous catheters (central lines). The complexities of patient man- agement in neonatal and pediatric intensive care units have Table 1. Applying Classification of Recommendations and Level of Evidence A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. Baltimore et al Infective Endocarditis in Childhood: 2015 Update 1489 increased the risk of IE in children with structurally normal hearts. 