The approach to treating febrile non-neutropenic hematooncologic patients with central venous catheters varies. We recently introduced once-daily administration of cefonicid and gentamicin for such children who were in good clinical condition and without focal signs of infection. Our 2-year experience of 125 episodes in 54 children is hereby reported. Absolute neutrophil counts were 550 to 16,700/mm3. Bacteremia occurred in 6.4% episodes: only in patients with Hickman/Broviac catheters and not in those with port-a-caths [8/37 (21.6%) vs. 0/17 patients, P=0.046; 8/86 (9.3%) vs. 0/39 episodes, P=0.056]. The pathogens were coagulase-negative staphylococci (3), Streptococcus pneumoniae (2), Pseudomonas aeruginosa and Klebsiella pneumoniae (1), methicillin-sensitive Staphylococcus aureus (1), and Streptococcus milleri (1). All patients remained in stable clinical condition and all, except for 2 who became neutropenic and 1 with S. aureus bacteremia who developed cellulitis, defervesced while on the empiric therapy. Three episodes could not be managed as outpatients. No adverse effects were observed. We conclude that our approach is efficacious and safe and, furthermore, that empiric antibiotic therapy may not be indicated for selected patients with port-a-caths. Future study of children with Hickman/Broviac catheters will evaluate the use of cefonicid alone.