Infection is the most common complication and cause of failure of cerebrospinal fluid (CSF) shunt devices used to control hydrocephalus. A male newborn was admitted for treatment of congenital occlusive hydrocephalus by means of a ventriculo-peritoneal shunt. A day later, the skin area around the site of insertion of ventriculo-peritoneal catheter was red and edematous. Intravenous ceftazidime and vancomycin were initiated. The shunt was removed but the external ventricular drain was preserved. Blood and CSF cultures showed Enterococcus faecalis sensitive to vancomycin, ciprofloxacin and gentamicin, but resistant to ampicillin. Intraventricular administration of vancomycin 10 mg/24 h was initiated through the external ventricular drain. Before the first dose of vancomycin intraventricularly, CSF levels were 19 mg/dL as a result of administration. On the third day of intraventricular dosing, vancomycin levels in CSF reached 388 mg/dL and protein levels were 1160 mg/dL. On the fifth day of intraventricular treatment the patient had clinically improved and was bacteriologically cured. However, in CSF, protein levels were 3300 mg/dL and vancomycin levels 201 mg/dL. In an attempt to prevent high and potentially toxic levels in CSF, the intraventricular dose of vancomycin should be individualized according to clinical response, bacteriological cultures, vancomycin levels in CSF, and surrogate markers of neurotoxicity, that is, eosinophilia and high protein levels in CSF.