Q. A 4-year-old girl with sickle cell disease presents to the emergency department with a temperature of 39.6 C (103.2 F). Other than irritability, the physical examination is unremarkable. Laboratory evaluations reveal a white blood cell count of 18,200/mm3, with 88% polymorphonuclear neutrophils, 10% lymphocytes, and 2% monocytes, and a hemoglobin of 7.6 g/dL. Which of the following is the most appropriate next step in management? A. Observe the child pending blood culture results B. Administer amoxicillin orally C. Administer ceftazidime and gentamicin intravenously D. Administer ceftriaxone intravenously E. Administer vancomycin and gentamicin intravenously Explanation: The answer is D. Children with sickle cell disease are at risk of serious bacterial infection and sepsis because they have impaired splenic function. Sepsis in these children is often caused by encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae type b. The course of the infection, if uncontrolled by appropriate antibiotic treatment, can be overwhelming and results in rapid deterioration and eventual death. Blood cultures, preferably two sets, should be obtained promptly before the initiation of antibiotic therapy. However, antibiotics should not be delayed while waiting for the culture results (choice A). Intravenous ceftriaxone is the most commonly used antibiotic in a febrile child with sickle cell disease. It is effective against both S. pneumoniae and H. influenzae. Orally administered amoxicillin (choice B) is not adequate for bacteremia or sepsis in a child with sickle cell disease and fever. Combined therapy of ceftazidime and gentamicin (choice C) is used against suspected Pseudomonas aeruginosa infection in patients with neutropenia or cystic fibrosis. Although combination therapy with vancomycin and gentamicin (choice E) covers a wide range of gram-positive and gram-negative organisms, it is not indicated in a febrile child with sickle cell disease.