Initial Assessment Sickle cell patients have a higher risk of bacterial infection than the general population due to functional asplenia, low serum immunoglobulin levels, and abnormal opsonization and complement activation The risk is highest for serious infections with encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Salmonella species, as well as S aureus and E coli Sepsis, meningitis, pneumonia, osteomyelitis, abscesses, and septic arthritis are all possible The use of oral penicillin prophylaxis until age and vaccination for H influenzae and S pneumoniae have decreased the rate of serious bacterial infection; however, infection remains a meaningful concern in the setting of an acutely ill, febrile patient with sickle cell anemia In one large retrospective study at a tertiary care center, the bacteremia rate in 1,118 acutely febrile patients with sickle cell was 0.8%; the nine cases of bacteremia included four cases of Salmonella, two S pneumoniae, two E coli, and one S aureus Management/Diagnostic Testing In the emergency department, a toxic-appearing febrile child with sickle cell disease requires careful and immediate evaluation, monitoring, fluid resuscitation, and rapid administration of antibiotics A pathway for the management of sickle cell disease with fever is available at https://www.chop.edu/clinical-pathway/sickle-cell-disease-withfever-clinical-pathway Obtain cultures of blood, and, if indicated, urine and spinal fluid Include a type and cross Do not delay antibiotic administration due to difficulty obtaining labs or performing procedures In regions with endemic resistant S pneumoniae strains, use vancomycin in addition to a third-generation cephalosporin Consider broader-spectrum antibiotics as indicated based on concern for abdominal process or for severe presentations As in other patients with reduced or absent splenic function, clinical deterioration may be extremely rapid The patient who arrives alert to the ED may become moribund and hypotensive within 30 minutes In the ill patient with sepsis, acidosis, or hypoxia, provide simple or exchange transfusions to decrease massive sickling, which can cause secondary organ damage Mortality from bacteremia may approach 20% to 30% Have a high level of suspicion for meningitis in the young, irritable child with sickle cell disease and unexplained fever Perform a lumbar puncture on toxic children and anyone with signs or symptoms of meningitis Use the same antibiotic therapy for meningitis as recommended for children with meningitis with hematologic disease Simple or exchange transfusion to lower the percentage of sickle hemoglobin may reduce the risk of intracerebral sickling in areas of brain swelling that can lead to infarction When hemoglobin S is less than 30% of the total hemoglobin, sickling is unlikely, and decisions regarding fluid management can be directed by the central nervous system findings as opposed to the need to ameliorate sickling The nontoxic, febrile child (temperature >38.5°C) with sickle cell disease requires a thorough history and physical examination Detailed history should focus on length,