Safety and Efficacy of Combined Prophylactic Intraventricular Administration of Vancomycin and Gentamicin on External Ventricular Drain-Related Infection Rate: A Four-Arm, Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract

External ventricular drain (EVD) placement is widely used in neurosurgery for managing elevated intracranial pressure, but EVD-related infections (ERIs) remain a serious complication. Current prophylactic strategies, including systemic antibiotics and coated catheters, offer inconsistent protection. This study evaluated the safety and efficacy of prophylactic intraventricular vancomycin and gentamicin, individually and in combination, to prevent ERIs. In a four-arm, randomized, double-blind, placebo-controlled trial, 200 patients requiring EVD placement were randomized into 4 groups: vancomycin with gentamicin (group VG), vancomycin (group V), gentamicin (group G), and normal saline as the placebo (group C). Multivariate regression analysis was also performed to identify potential independent predictors of ERI and estimate odds ratios (ORs). No serious adverse event attributable to the study drugs was found throughout the present study. During the study period, a total of 12 (24.0%), 7 (14.0%), 8 (16.0%), and 2 (4.0%) patients developed ERI in groups C, G, V, and VG, respectively. The incidence rate of ERI was significantly different among the study groups (P = .042). In addition, a statistically significant difference was noted among the study groups in duration of EVD placement (P = .032), intensive care unit stay (P = .015), and hospitalization (P = .022), as well as catheter replacements (P = .021) and time-to-infection (P = .045). Multivariate analysis confirmed that combination of vancomycin and gentamicin significantly reduced (OR = 0.083 [95% CI, 0.014-0.471], P = .005) infection odds, while subarachnoid hemorrhage/intraventricular hemorrhage (OR = 6.5 [95% CI 1.7-25.0], P = .006) and immunosuppression (OR = 21.9 [95% CI, 5.0-95.2], P < .001) were independent risk factors for ERI. Single-dose prophylactic intraventricular vancomycin-gentamicin combination significantly reduces ERI incidence and improves clinical outcomes, offering a potentially cost-saving and scalable infection control strategy particularly in resource-limited conditions. Future multicenter studies are warranted to confirm these findings.