Ceftriaxone Prophylaxis may Prevent ventilator associated pneumonia in Acute Brain Injury Patients

In a significant leap forward, a recent multicenter study, PROPHY-VAP, has unveiled a potential breakthrough in the prevention of ventilator-associated pneumonia (VAP) among patients with acute brain injury. The trial, conducted in nine intensive care units across eight French university hospitals, focused on the impact of a single, early dose of the antibiotic ceftriaxone on the incidence of early VAP in comatose adults requiring mechanical ventilation.

The trial results were published in the journal The Lancet: Respiratory Medicine.

Patients with acute brain injury undergoing mechanical ventilation face an elevated risk of developing VAP, a complication that can exacerbate their condition and lead to severe consequences. The PROPHY-VAP trial aimed to address the ongoing debate regarding the effectiveness of short-term antibiotic prophylaxis in preventing VAP in this specific and vulnerable patient population.

This multicenter, randomized, double-blind, placebo-controlled trial enrolled comatose adult patients (Glasgow Coma Scale score [GCS] ≤12) aged 18 years or older, requiring mechanical ventilation for at least 48 hours post-acute brain injury. The participants were randomly assigned to receive either a single, early intravenous dose of ceftriaxone 2 g or a placebo within 12 hours of tracheal intubation. The primary outcome measured was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by assessors who were masked to the treatment.

Key Findings and Impact:

• About 345 patients were enrolled in the study, with 330 receiving the allocated intervention.
• The final analysis included 319 participants, and the results were striking.
• The incidence of early VAP was significantly lower in the ceftriaxone group compared to the placebo group (14% vs. 32%).
• The hazard ratio of 0.60 (95% CI 0.38–0.95) indicated a substantial reduction in the risk of developing VAP with the administration of a single ceftriaxone dose.
• Adjudication confirmed 93 cases of VAP, with 74 classified as early infections.

This groundbreaking study underscores the potential of a single, early dose of ceftriaxone in significantly reducing the risk of early VAP among patients with acute brain injury requiring mechanical ventilation. The findings suggest a promising addition to comprehensive prevention bundles for VAP in this specific patient population. Importantly, the study revealed no microbiological impact or adverse effects attributable to ceftriaxone, supporting its safety and efficacy. As researchers continue to refine protocols for VAP prevention, particularly in critically ill patients with acute brain injury, this study paves the way for potential transformative changes in clinical practice and improved patient outcomes.

Further reading: Dahyot-Fizelier C, Lasocki S, Kerforne T, et al. Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial. Lancet Respir Med. Published online January 19, 2024. doi:10.1016/S2213-2600(23)00471-X