Ceftriaxone lessens early ventilator-associated pneumonia in patients with brain injury

Key takeaways:

• Fewer early ventilator-associated pneumonia cases occurred among patients with brain injury receiving ceftriaxone vs. placebo.
• Patients receiving ceftriaxone also had more antibiotic- and ventilator-free days.

One dose of ceftriaxone lowered the risk for ventilator-associated pneumonia within the first week of mechanical ventilation among patients with acute brain injury, according to results published in The Lancet Respiratory Medicine.

In addition to this publication, findings from this study were presented at this year’s Society of Critical Care Medicine’s Critical Care Congress.

“[The] PROPHY-VAP trial confirms the protective effect of a single dose of two grams of ceftriaxone without application of [selective digestive decontamination] in brain-injured patients,” Claire Dahyot-Fizelier, MD, PhD, professor of anesthesia and intensive care at University of Poitiers in France, said during her presentation at the meeting.

In a multicenter, randomized, double-blind, placebo-controlled, assessor-masked superiority trial (PROPHY-VAP), Dahyot-Fizelier and colleagues assessed 319 adults (mean age, 57 years; 48% women) in the ICU with acute brain injury who needed to receive mechanical ventilation for a minimum of 48 hours to see if one dose of 2 g intravenous ceftriaxone prevents the development of early ventilator-associated pneumonia (VAP).

Of the total cohort, 162 patients received the dose of ceftriaxone less than 12 hours after intubation, and 157 patients received the placebo dose during the same timeframe.

A central adjudication committee reviewed 160 reported cases of VAP and confirmed VAP in 93 of them. Many of these cases (74 cases; 82%) occurred between the second and seventh day of mechanical ventilation.

Among those who developed VAP, a median of 5 days passed between intubation and the infection. In the ceftriaxone group, the median time to infection was 5 days, whereas the median time was 4 days in the placebo group, according to researchers.

Fewer cases of early VAP occurred among those who received ceftriaxone vs. placebo (23; 14% vs. 51; 32%), demonstrating that the single ceftriaxone dose significantly reduced the risk for early VAP (HR = 0.6; 95% CI, 0.38-0.95).

In addition to early VAP incidence, researchers looked at several secondary endpoints between the two groups.

When evaluating all types of VAP at day 28, researchers again found fewer cases in the ceftriaxone group vs. the placebo group (20% vs. 36%), as well as a decreased risk for this outcome with ceftriaxone (HR = 0.53; 95% CI, 0.31-0.92).

The median number of ventilator-free days was significantly higher among those who received ceftriaxone vs. placebo (9 days vs. 5 days), as was the median number of antibiotic-free days (21 days vs. 15 days), Dahyot-Fizelier said during her presentation.

Researchers further found that the ceftriaxone group had significantly more ICU-free days (median, 34 days vs. 26 days; P = .0033) and hospital-free days (median, 23 days vs. 8 days; P = .005) by day 60.

Between the two groups, a significantly smaller proportion of patients died from the ceftriaxone group at day 28 (15% vs. 25%; HR = 0.62; 95% CI, 0.39-0.97).

Researchers focused on patients with rectal swabs to assess microbiological findings, and this included 59 patients from the ceftriaxone group and 56 patients from the placebo group. Notably, two patients receiving ceftriaxone had ESBL-producing Enterobacteriaceae acquisition, whereas this was not found among patients receiving placebo.

Further, a Clostridium difficile infection appeared in two patients receiving placebo and one patient receiving ceftriaxone.

Although researchers observed 39 severe adverse events in the cohort receiving ceftriaxone (90 in the total cohort), none of these events could be attributable to the dose.

“[This trial] confirmed the protection of a patient receiving ceftriaxone against early VAP [and] all types of VAP at day 28; antibiotic and mechanical ventilation exposition at day 28; mortality at day 28 and ICU and hospital exposure at day 60,” Dahyot-Fizelier said during her presentation.

Reference:

• Dahyot-Fizelier C. Thought leader: Late-breaking studies that will change your practice. Presented at: Society of Critical Care Medicine’s Critical Care Congress; Jan. 21-23, 2024; Phoenix.