Individuals recovering from acute brain injuries have increased susceptibility to ventilator-associated pneumonia (VAP), a significant concern for medical practitioners due to increased incidences ranging from 20% to 71% in severe trauma patients and 28% to 76% in stroke patients. The debate surrounding short-term antibiotic prophylaxis as a preventive measure against VAP in this population prompted the PROPHY-VAP trial, conducted by Fizelier et al. and published in the Journal of Lancet Respiratory Medicine. Spanning nine intensive care units in eight French university hospitals, the trial concluded on the effectiveness of early, single dose of ceftriaxone on early VAP incidence in mechanically ventilated patients with severe brain injuries.
The trial involved randomly assigning comatose adult patients (Glasgow Coma Scale score [GCS] ≤12) aged 18 years or older to receive either intravenous ceftriaxone 2 g or a placebo within 12 hours after tracheal intubation. The participants did not undergo selective oropharyngeal and digestive tract decontamination. The primary outcome measured was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, as confirmed by masked assessors. The PROPHY-VAP trial included 345 randomized patients meeting brain injury criteria.
The study revealed a significant reduction in the confirmed incidence of early VAP among patients who received an early dose of ceftriaxone compared to those assigned a saline placebo. Specifically, the incidence was 14% in the ceftriaxone group versus 32% in the placebo group. By the 28th day, the risk of developing all types of VAP remained lower in the ceftriaxone group (20% vs 36%). Additionally, the ceftriaxone group exhibited a lower mortality rate (15% vs 25%) and more ICU-free days (34 vs 26) and hospital-free days (23 vs 8). Three patients developed Clostridium difficile infection during the trial, with two in the placebo group and one in the ceftriaxone group. Adverse events were monitored, with 194 recorded during the trial, and none were attributed to ceftriaxone. No significant microbiological impact was associated with ceftriaxone treatment, suggesting promise in reducing bacterial resistance.
Fizelier and colleagues emphasized the protective effect of a single 2 g dose of ceftriaxone in brain-injured patients without resorting to selective digestive tract decontamination. Acknowledging the significant threat that VAP poses to ICU patients, particularly those with acute brain injuries, the researchers highlighted its implications, including increased morbidity, mortality, secondary insults in brain-injured patients, exposure to antibiotics, and mechanical ventilation. VAP is also linked to prolonged ICU and hospital stays with higher associated costs.
Early ceftriaxone administration could be a proactive strategy in improving the respiratory health and overall prognosis of this vulnerable patient population. These findings provide a significant step forward in enhancing evidence-based interventions and shaping future treatment protocols for post-acute brain injury care.
Reference
Dahyot-Fizelier C, Lasocki S, Kerforne T, Perrigault PF, Geeraerts T, Asehnoune K, 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. 2024 Jan 19;S2213-2600(23)00471-X.