medwireNews: A single dose of the antibiotic ceftriaxone significantly reduces the risk for early-onset ventilator-associated pneumonia (VAP) in individuals with head trauma, stroke, or subarachnoid hemorrhage, show results from the multicenter, double-blind PROPHY-VAP trial.
Among the participants, all of whom were predicted to require mechanical ventilation for at least 48 hours after brain injury, the incidence of early VAP was a significant 40% lower in 162 patients who were randomly assigned to receive ceftriaxone than in 157 who instead received placebo, at rates of 14% versus 32%.
Treatment with ceftriaxone also significantly reduced rates of “exposure to ventilation, exposure to antibiotics, prolonged ICU [intensive care unit] and hospital stay, and mortality, with no safety concerns,” note Claire Dahyot-Fizelier, from the University of Poitiers in France, and associates.
The study cohort comprised comatose individuals aged a mean of 57 years (48% women) with a Glasgow Coma Scale Score of 12 points or below, who received either a 30-minute administration of intravenous ceftriaxone 2 g or saline in the 12 hours following tracheal intubation. The study took place in nine ICUs across eight French university hospitals.
The participants were assessed by ICU physicians several times a day for 28 days for VAP occurrence, write Dahyot-Fizelier and team in The Lancet Respiratory Medicine.
A total of 93 cases of VAP were confirmed by an adjudication process, with early VAP, occurring within the second to seventh day after commencing mechanical ventilation, representing 82% of cases, report the researchers.
At day 28, they found that patients who received ceftriaxone had a significant 38% reduced risk for developing any kind of VAP than those given placebo (20 vs 36%) and had gone significantly longer without being exposed to mechanical ventilation (median 9 vs 5 days) or antibiotics (median 21 vs 15 days). Mortality rates were also significantly lower in the ceftriaxone than the placebo group, at 15% versus 25%, corresponding to a hazard ratio in favor of ceftriaxone of 0.62.
ICU and hospital stays in the 60 days following treatment were more often avoided by patients given ceftriaxone than those given placebo. The former group had a median 34 ICU-free days and 23 hospital-free days, compared with respective medians of 26 days and 8 days in the latter group.
Overall, 194 adverse events, including cutaneous abscess, ischemic stroke, cardiac arrest, and septic shock, occurred in 152 patients, including 90 severe cases – 39 in the ceftriaxone group and 51 in the placebo.
However, “[a]ll serious events were attributed to the initial disease and not to trial intervention,” write the researchers, who conclude: “Our results suggest that early administration of 2 g ceftriaxone could be applied to all patients with brain injury who require mechanical ventilation.”
In a comment accompanying the study, Michael Klompas, from Harvard Medical School in Boston, Massachusetts, USA, remarks that many European centers are reluctant to introduce prophylactic antibiotics into routine care for critically ill patients “because of the fear of selecting for resistant organisms at both the individual level and the population level.”
In addition, there is a possibility of introducing antibiotics to an uninfected patient without “certainty of parallel benefit,” he states.
However, Klompas believes that Dahyot-Fizelier and colleagues’ findings help “focus the question on a subset of patients at particularly high risk of VAP and poor outcomes.”
He comments: “If further studies confirm benefits without harm in patients with acute brain injuries, this might be the ICU subpopulation in whom we can begin to use antibiotic prophylaxis more broadly and therein advance our collective experience, understanding, and comfort level with this controversial but potentially life-saving prevention strategy.”
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