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Profound evidence substantiates significantly reduced risk of catheter-related infections with prophylactic use of rifampin- and clindamycin-impregnated silicone catheters (Bactiseal(®), Codman Johnson & Johnson, Raynham, MA, USA) for external ventricular drainage (EVD). However, whether Bactiseal(®)-EVD (B-EVD) influences the treatment of EVD-related ventriculitis remains controversial. We performed a retrospective analysis of patients who developed ventriculitis after EVD or ventriculoperitoneal (VP) shunt placement and consequently underwent either placement of B-EVD (group 1) or a standard non-antibiotic-impregnated EVD (group 2). Analyzed parameters included demographic and clinical data, hospitalization time, time until remission of the infection parameters, detection of new bacterial resistance on antibiograms, and clinical outcome in terms of the modified Rankin scale (mRS). Time until remission of cerebrospinal fluid (CSF) pleocytosis was significantly longer in patients undergoing B-EVD (8 ± 3.8 days; n = 15; group 1) than in patients who underwent standard EVD (5.1 ± 1.8 days; n = 10; group 2). There was no significant difference between both groups for the time until polymorphonuclear cells dropped below 50% of peak value (5.8 ± 1.6 vs. 4.1 ± 2.9 days), CRP dropped below 10 mg/l (4.2 ± 3.5 vs. 5.6 ± 3.3 days), the time of plasma neutrophil remission (5.7 ± 2.6 vs. 5.3 ± 3.2 days) and hospitalization time (28 ± 12.5 vs. 35 ± 19.4 days). The mRS for both groups was 2. Development of new antibiotic resistance did not occur in either group. This retrospective pilot study indicates that B-EVD might have no major advantage in the management of EVD or VP-shunt-related ventriculitis. Based on published reports and the results of this study, data support only the prophylactic use of B-EVD for prevention of EVD-related infections. Prospective randomized clinical trials are warranted to further evaluate the role of B-EVD in the treatment of ventriculitis.