There are increasing reports of citrobacter central nervous system infections in neonates. These organisms cause brain abcesses in a high percentage of patients. They may be resistant to commonly used antibiotics. We report a term male infant with underlying meningo-myelocoele and hydrocephalus in whom Citrobacter diversus meningitis and ventriculitis developed. Initial antibiotic therapy including intraventricular amikacin failed to sterilize the ventricles or alter a deteriorating clinical course. Adding intravenous trimethoprim-sulfamethoxazole to the therapeutic regimen resulted in reversal of a progressively worsening condition and eventual recovery. Trimethoprim-sulfamethoxazole should be considered as a potentially useful alternative antibiotic for susceptible central nervous system infections.