Infection causes major morbidity and mortality in patients with cerebrospinal fluid (CSF) shunts. The prognosis of CSF shunt infections caused by Gram-negative bacteria (GNB) has been thought to be particularly poor. The authors reviewed all GNB shunt infections treated at Children's Memorial Hospital from January 1986 to January 1990 (n = 23). Of these infections 20 (87%) occurred within 4 weeks after shunt revision (median, 10 days). The most frequent symptoms were fever, lethargy, and irritability; the illness was not severe in the majority of these patients. Escherichia coli was isolated from 12 of 23 patients (52%), Klebsiella pneumoniae from 5 (22%), and mixed GNB from 3 (13%) patients. Initial treatment always included immediate shunt removal, externalized ventricular drainage, and intravenous antibiotics. Extraventricular drainage revision and/or intraventricular antibiotics were required in four patients whose CSF cultures were persistently positive for GNB. At admission, these patients had CSF glucose levels of < 10 mg/dl and CSF positive for GNB by Gram's stain. The overall cure rate was 100%, and no recurrence was observed; however, a subsequent infection with a different organism developed in four patients. Only 2 of 19 patients (11%) who were followed up suffered apparent CNS damage. One patient died of unrelated causes shortly after treatment. Our findings indicate that 1) patients with GNB CSF shunt infections often appear relatively well at presentation; 2) CSF positive for GNB by Gram's stain and very low CSF glucose levels predict continued positive CSF cultures, despite appropriate antibiotic therapy; and 3) GNB CSF shunt infections can be successfully treated by prompt shunt removal, extraventricular drainage, and intravenous antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)