In patients who are not acutely ill and whose blood cultures remain negative, withholding antibiotic drugs for 48 hours while additional blood cultures are obtained may be considered to determine the cause of IE (Class IIb; Level of Evidence C). 4. In patients with acute IE who are severely ill and unstable, 3 separate venipunctures for blood cul- tures should be performed over a short period such as 1 to 2 hours (Table 3) and empirical antibiotic therapy initiated (Class I; Level of Evidence C). 5. If fastidious or unusual organisms are suspected, the director of the microbiology laboratory or a consultant in pediatric infectious diseases should be consulted for help in diagnosis and especially for guidance on molecular pathogen identification and when use of serological testing is likely to be benefi- cial (Class I; Level of Evidence C). 6. Culture of arterial blood is not more useful than venipuncture because it does not increase yield over venous blood cultures, but it is acceptable if only arterial blood samples are able to be obtained (Class III, No Benefit; Level of Evidence B). Pathogenic Agents Isolated From Blood Cultures The very large majority of organisms that cause IE in chil- dren are Gram-positive cocci (Table 5), including VGS (eg, Streptococcus sanguis, S mitis group, S mutans), staphy- lococci (both S aureus and coagulase-negative staphylo- cocci), -hemolytic streptococci, and enterococci.11,13,24,81 Enterococcal endocarditis is relatively less common in children than in adults. Less frequently, other organ- isms such as the HACEK group of organisms (HACEK indicates Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are implicated. After the first year of life, VGS are generally the most frequently isolated organisms in patients with IE caused by underlying congenital heart disease. 