PROPHY-VAP Trial

Ventilator-associated pneumonia (VAP) is a significant concern in intensive care units (ICU), especially prevalent among brain-injured patients who are mechanically ventilated. With VAP incidence rates ranging from 22% to 71%, depending on the study, and brain injury being a notable independent risk factor, the prevention of this infection is paramount. Current standard of care includes a set of measures aiming to reduce the incidence of VAP; however, the challenge of early versus late onset VAP and the associated risk of multi-drug resistant organisms necessitate ongoing research and innovation in prophylactic strategies. The PROPHY-VAP trial is a pivotal study that explores the use of prophylactic antibiotics, specifically ceftriaxone, to prevent early-onset VAP in brain-injured patients. By addressing the controversial cut-off for early VAP onset in this population and considering the unique susceptibility profile of their infections, this trial holds significant importance for enhancing patient outcomes and refining ICU protocols.

PROPHY-VAP was a multicentre, randomized, double-blind, placebo-controlled trial conducted in nine French ICUs. The study enrolled comatose adult patients (Glasgow Coma Scale score ≤12) requiring mechanical ventilation post-acute brain injury. Patients were randomly assigned to receive either intravenous ceftriaxone 2 g or a placebo within 12 hours of tracheal intubation. The primary outcome was the incidence of early VAP (2nd to 7th day of mechanical ventilation). The study excluded patients with high death risk within 48 hours, previous hospitalizations for coma, contraindications to beta-lactams, and those receiving antibiotics for pre-existing infections.

• The PROPHY-VAP trial was conducted over a period spanning from October 14, 2015, to May 27, 2020, during which 345 patients were randomized in a 1:1 ratio to receive either ceftriaxone (171 patients) or placebo (174 patients). The study observed a marked reduction in the incidence of early VAP in the ceftriaxone group, with only 14% (23 patients) developing the infection compared to 32% (51 patients) in the placebo group, translating to a hazard ratio of 0.60. This significant decrease in early-onset VAP incidence, demonstrated in a double-blind, placebo-controlled setting, suggests that a single dose of ceftriaxone can be an effective prophylactic intervention in brain-injured patients requiring mechanical ventilation.

A detailed analysis of the patient demographics within the trial revealed that out of the 319 patients included in the analysis, 166 were men and 153 were women. Adjudication confirmed a total of 93 cases of VAP, of which 74 were early infections. Importantly, the study reported no increase in multi-drug resistant organisms or adverse effects attributable to the administration of ceftriaxone. These results indicate that the intervention was not only efficacious in reducing the incidence of early VAP but also safe for the patients, with no additional risk of fostering antibiotic resistance. The authors report that these findings provide a strong argument for the inclusion of a single dose of ceftriaxone in VAP prevention bundles for this patient population.