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To prospectively identify all cases of bacteremia in children with sickle cell disease (SCD), establish time to positivity for various microorganisms, correlate clinical findings with microbiology data, and determine the antibiotic resistance pattern of the pneumococcal isolates.All positive blood cultures from children with SCD followed at the Children's Hospital of Philadelphia from January 1993 through May 2001 were included. Isolates were classified as pathogen or contaminant. Demographic and clinical information was abstracted from the medical records. Time to positivity and antibiotic resistance data were generated in the microbiology laboratory.One hundred forty-one positive blood culture bottles were obtained during distinct febrile episodes. Thirty-nine percent contained pathogens and 61% contained contaminants. The average time to positivity was 17.1 hours in the pathogen group and 29.5 hours in the contaminant group (P < 0.0001). Streptococcus pneumoniae was the most common pathogen (42% of total), with a mean patient age of 3.5 years. Gram-negative rods were the second most common organism (28% of total), with a mean patient age of 8.1 years. Thirty-one percent of the pneumococcal isolates were resistant to penicillin. Thirty-five percent of the pneumococcal isolates grew from children with a focus of infection. Acute chest syndrome was noted in 26% of patients with a positive blood culture for S. pneumoniae. Sixty-seven percent of Salmonella isolates and 50% of Staphylococcus aureus isolates grew from patients who developed osteomyelitis.The average time to positivity for pathogens can be used in conjunction with other factors to determine the length of observation required for children with SCD who present with febrile illness. Chest radiographs should be obtained on children with SCD who are bacteremic with S. pneumoniae. Bone scans should be obtained on children with SCD who are bacteremic with Salmonella or S. aureus.