This report is limited to patients with a single cerebrospinal fluid (CSF) shunt infected by a single organism, and compares two treatment protocols. In the initial protocol (1975-1991), patients underwent removal of the shunt system and received intravenous and intraventricular antibiotics. Intraventricular antibiotics were administered twice daily to those with external ventricular drainage. When CSF was cultured 48 h off all antibiotics and found to be sterile at 24 h of incubation, a new shunt was inserted. Follow-up CSF cultures were obtained in all patients between 1-6 months following placement of the new shunt. There were 25 patients (ages 1 month to 16 years; mean +/- SD: 23 +/- 4.0 months). CSF obtained from the shunt yielded the following: Staphylococcus epidermidis (19), Staphylococcus aureus (2), Streptococcus species (2), Serratia marcescens (1), and Propionebacterium species (1). The duration of intravenous antibiotics was 7-12 days (mean +/- SD: 9.7 +/- 1.3 days), and intraventricular antibiotic therapy was 6.2 +/- 1.7 days. Total hospital stay was 15.2 +/- 2.3 days. The follow-up period was 7.7 +/- 3.6 years. Following the initial protocol in another 15 patients (1992-2004), the treatment regime was modified in that intraventricular antibiotics were administered once daily in patients with external ventricular drainage, and the CSF was cultured at 24 h off antibiotics, instead of 48 h. Results were similar to the initial protocol with respect to days of antibiotic therapy and hospital stay. Based on our retrospective nonrandomized series, we believe patients with a single shunt and noncompartmentalized hydrocephalus can be successfully treated without a prolonged antibiotic course and lengthy hospital stay.