Background <p>The effectiveness of antibiotic-impregnated catheters (AIC) compared to standard catheters (SC) as external ventricular drains (EVD) for preventing EVD-related infections (ERI) is debated. In this study, we aimed to analyze the impact of a shift from AIC to SC, and so a de-escalation strategy, on ERI incidence rate.</p> Methods <p>This is a single-center before-and-after analysis of prospectively recorded data from consecutive patients treated in a French tertiary care hospital neurological intensive care unit from 2015 to 2020. Standard EVD handling procedure remained unchanged over study period, except for the first line drain, which was switched from AIC to SC in 2019. The main outcome was the difference in the incidence of ERI.</p> Results <p>Data from 510 consecutive patients (348 AIC, 162 SC) were analyzed. AIC use was associated with a lower incidence of ERI (2.6% vs 8.0% of ERI, 2.4 vs 6.8 ERI for 1000 catheterization days) and a delay in its onset (median delay from insertion of 11.0 [7.0–16.0] vs 7.0 [4.0–12.0] days, subdistribution hazard ratio sHR 0.32 [0.14–0.76], during follow-up period, <i>p</i> = 0.010). The presence of a cutaneous leakage, manipulations of EVD proximal stopcock, prolonged drainage duration and withdrawal motive were also associated with ERI diagnosis. Identified microorganisms according to Gram-staining did not differ with respect to catheter type, but the proportion of skin commensals is reduced using AIC (49.1 vs 68.9%, <i>p</i> = 0.047).</p> Conclusions <p>Our findings suggest that AIC use as first intention catheter for CSF drainage was associated with a lower and delayed incidence of ERI.</p> <p>OTHERS: No funding was received for this study.</p>