Prophylactic Antibiotics in Adults With Acute Brain Injury Who Are Invasively Ventilated in the ICU: A Systematic Review and Meta-Analysis

Background: Lower respiratory tract infections are common in patients receiving invasive mechanical ventilation in an ICU after an acute brain injury and may have deleterious consequences.

Research question: In adults with acute brain injury receiving invasive mechanical ventilation in an ICU, is the administration of prophylactic parenteral antibiotics, compared with placebo or usual care, associated with reduced mortality?

Study design and methods: We conducted a systematic review and meta-analysis. We searched for randomized clinical trials (RCTs) in electronic databases, as well as unpublished trials. The primary outcome was hospital mortality, and secondary outcomes included the incidence of ventilator-associated pneumonia, ICU length of stay, and duration of mechanical ventilation. We used a random effects model to estimate the pooled risk ratio (RR) with corresponding 95% CI for binary outcomes and the mean difference (MD) with 95% CI for continuous outcomes. Certainty of evidence was evaluated using Grading of Recommendations Assessment Development and Evaluation methods.

Results: One thousand seven hundred twenty-eight reports of studies were screened, with 7 RCTs recruiting 835 participants included. No trials were adjudicated as having a high risk of bias. The pooled estimated RR for mortality associated with the use of prophylactic antibiotics was 0.91 (95% CI, 0.70-1.17; P = .39; low certainty). The pooled estimated RR for ventilator-associated pneumonia was 0.56 (95% CI, 0.35-0.89; low certainty). The pooled estimated duration of mechanical ventilation for those allocated to prophylactic antibiotics compared with control participants (MD, -2.0 days; 95% CI, -6.1 to 2.1 days; very low certainty) and duration of ICU admission (MD, -2.2 days; 95% CI, -5.4 to 1.1 days; very low certainty) were similar.

Interpretation: Current evidence from randomized clinical trials does not provide definitive evidence regarding the effect of prophylactic antibiotics on mortality in patients receiving invasive mechanical ventilation in the ICU.

Clinical trial registry: International Prospective Register of Systematic Reviews; No.: CRD42023424732; URL: https://www.crd.york.ac.uk/prospero/.