Early Antibiotic Prophylaxis in Comatose Patients to Prevent Early-Onset Ventilator-Associated Pneumonia: A Systematic Review and Bayesian Meta-Analysis

: Background: Early-onset ventilator-associated pneumonia (EO-VAP) is a frequent complication in comatose patients requiring endotracheal intubation. This systematic review and Bayesian meta-analysis assesses the effectiveness of antibiotic prophylaxis in preventing EO-VAP in this population. Methods: Randomized controlled trials (RCTs) and observational studies enrolling adult comatose patients (GCS ≤ 8) requiring endotracheal intubation and reporting EO-VAP incidence, late-onset VAP, ICU mortality, 28-day mortality, or ICU length of stay were included. Studies without a control group or not focused on comatose patients were excluded. Following PRISMA 2020 guidelines, a comprehensive search was conducted across three databases from inception to 31 March 2026. Risk of bias was assessed using the RoB2 tool for RCTs and the ROBINS-I tool for observational studies. Results: In accordance with Cochrane Handbook recommendations, only RCTs were included in the quantitative analysis. Five RCTs (735 patients) demonstrated a significant reduction in EO-VAP incidence with antibiotic prophylaxis (RR 0.46 [95% CI: 0.35-0.59], p = 0.001, I2 = 0%), with the strongest effect in neurological patients (RR 0.41 [95% CI: 0.32-0.53], NNT = 5.4). No significant effect on mortality was demonstrated. Bayesian analysis confirmed these findings (posterior median RR 0.44 [95% CrI: 0.33-0.59], P(benefit) = 100%). Limitations: The analysis was limited by the small number of RCTs and the absence of data on antimicrobial resistance. Conclusions: Antibiotic prophylaxis reduces EO-VAP incidence in comatose patients, particularly neurological patients. A general recommendation cannot currently be made pending further evidence on mortality and antimicrobial resistance. Registration: This systematic review was prospectively registered on PROSPERO (CRD42024580280).