Associations Between Prophylactic IV Antibiotics and Outcomes in Patients With Acute Severe Brain Injury Who Require Mechanical Ventilation: Systematic Review and Meta-Analysis

OBJECTIVES: To evaluate the impact of prophylactic IV antibiotics on ventilator-associated pneumonia (VAP) and other outcomes in critically ill patients with acute brain injury. DATA SOURCES: We searched PubMed, Embase, CINAHL, and other databases without language restrictions from inception to November 1, 2024. STUDY SELECTION: We included randomized trials that enrolled patients 16 years old or older with severe acute brain injury (e.g., trauma, stroke, and hypoxia) and compared prophylactic IV antibiotics to placebo or no antibiotics. Studies evaluating oral or gastric antibiotic prophylaxis were excluded. DATA EXTRACTION: Two reviewers independently evaluated study characteristics, pneumonia rates, mortality, duration of mechanical ventilation, ICU and hospital length of stay, post-admission bacteremia, antibiotic utilization, neurologic outcomes, and adverse events including antibiotic-resistance and Clostridioides difficile infections. Quality was assessed using the Cochrane risk-of-bias template. Studies were synthesized using inverse-variance random-effects models. Sensitivity analyses included stratifications by risk-of-bias, Glasgow Coma Scale, antibiotic duration, and mechanism of brain injury. DATA SYNTHESIS: We identified seven eligible trials (827 patients). Prophylactic antibiotics were associated with less VAP (risk ratio [RR], 0.61; 95% CI, 0.47-0.78; I2 = 23%) but not with changes in duration of mechanical ventilation (mean difference [MD], -0.45; 95% CI, -1.63 to +0.74), ICU length of stay (MD, -1.76 d; 95% CI, -3.94 to +0.42 d), hospital mortality (RR, 0.91; 95% CI, 0.74-1.12), or long-term neurologic outcomes. On stratification by mechanism of injury, antibiotic prophylaxis was associated with significantly less VAP, shorter ICU length of stay, and a trend toward lower mortality in patients with structural but not hypoxic brain injuries. Other sensitivity analyses were consistent with the primary findings. CONCLUSIONS: Among critically ill patients with acute brain injury, prophylactic IV antibiotics were associated with less VAP but not with changes in length of stay, mortality, or neurologic outcomes. Patients with structural brain injuries may benefit more than those with hypoxic brain injury but further studies are needed to confirm or refute this possibility.