ORIGINAL ARTICLES Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia Gary R. Fieisher, MD, Norman Rosenberg, DO, Robert Vinci, MD, Joel Steinberg, MD, Keith Powell, MD, Cynthia Christy, MD, Douglas A. Boenning, MD, Gary Overturf, MD, David Jaffe, MD, and Richard Platt, MD From the Departments of Pediatrics, Harvard Medical School, Boston, Massachusetts, Wayne State University School of Medicine, Detroit, Michigan, Boston University School of Medicine, Boston, Massachusetts, University of Texas Southwestern Medical School, Dallas, University of Rochester School of Medicine and Dentistry, Rochester, New York, George Washington University School of Medicine, Washington, D.C., University of New Mexico School of Medicine, Albuquerque, and Washington University School of Medicine, St. Louis, Missouri, and the De- partment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts Because studies of the treatment of children with occult bacteremia have yielded conflicting results, we compared ceftriaxone with amoxicillin for ther- apy. Inclusion criteria were age 3 to 36 months, temperature ___39 ~ C, an acute febrile illness with no focal findings or with otitis media (6/10 centers), and cul- ture of blood. Subjects were randomly assigned to receive either ceftriaxone, 50 mg/kg intramuscularly, or amoxicillin, 20 mg/kg/dose orally for six doses. Of 6733 patients enrolled, 195 had bacteremia and 192 were evaluable: 164 Strep- tococcus pneumoniae, 9 Haemophilus influenzae type b, 7 Salmonella, 2 Neisseria meningitidis, and 10 other. After treatment, three patients receiving amoxicillin had the same organism isolated from their blood (two H. influenzae type b, one Salmonella) and two from the spinal fluid (two H. influenzae type b), compared with none given ceftriaxone. Probable or definite infections occurred in three children treated with ceftriaxone and six given amoxicillin (adjusted odds ratio 0.43, 95% confidence interval 0.08 to 1.82, p = 0.31). The five children with definite bacterial infections (three meningitis, one pneumonia, one sepsis) received amoxicillin (adjusted odds ratio 0.00, 95% confidence interval 0.00 to 0,52, p = 0.02). Fever persisted less often with ceftriaxone (adjusted odds ratio 0.52, 95% confidence interval 0.28 to 0,94, p = 0.04). Although the difference in total infections was not significant, ceftriaxone eradicated bacteremia, pre- ventedsignificantly more definite focal bacterial complications, and was associated with less persistent fever. (J PEDIATR 1994;124:504-12) Supported in part by a grant from Hoffmann-LaRoche. Submitted for publication April 19, 1993; accepted Nov. 8, 1993 Reprint requests: Gary R. Fleisher, MD, Children's Hospital, 300 Longwood Ave., Boston, MA 02115. Copyright | 1994 by Mosby-Year Book, Inc. 0022-3476/94/$3.00 + 0 9/20/52687 Bacteremia with pathogenic microorganisms occurs in 3% to 7% of young children with high fever and no apparent source of serious infection, 19 and may lead to focal sequelae, sepsis, and/or death. 1~ The optimal treatment for children with known or suspected occult bacteremia has not been established. 1~ Despite this uncertainty, some 504