Severe central nervous system infections (CNSI), including community-acquired CNSI (CA-CNSI) and healthcare-associated ventriculitis and meningitis (HAVM), present high morbidity and mortality. Intraventricular antibiotic treatment (IVT) is advisable for these infections, though evidence is limited. We retrospectively analyzed data on 27 patients who received IVT for severe CA-CNSI and HAVM over 10 years, assessing clinical and paraclinical features, such as baseline severity and functional outcome, antibiotics, microbiological and laboratory data. Comparisons were made between patients affected by CNSI and HAVM and those with favorable and unfavorable outcomes, based on the modified Rankin scale. Gram-positive organisms dominated in CA-CNSI (64%), while gram-negative organisms were more frequent in HAVM (64%). Patients received a median of 30 days of intravenous antibiotics and 11 days of IVT, with no significant difference between CA-CNSI and HAVM. IVT-associated toxicity was rare. Patients with favorable outcomes (64%) had higher initial cerebrospinal fluid- white blood cell count (CSF-WBC), that decreased more rapidly than in patients with unfavorable outcomes. CSF-WBC dynamics did not differ between CA-CNSI and HAVM patients. Rapid decline in CSF-WBC after initiation of IVT was associated with favorable outcome. Despite severe neurological impairment at admission, most survivors achieved favorable long-term outcomes.