medwireNews: The risk for developing ventilator-associated pneumonia is significantly reduced in critically ill adults if they are given a 3-day course of the inhaled antibiotic amikacin, show results from the AMIKINHAL trial.
During the 28-day follow-up of 847 patients who had required at least 72 hours of mechanical ventilation, a first episode of ventilator-associated pneumonia occurred in 15% of 417 patients randomly assigned to receive amikacin 20 mg/kg of ideal body weight and 22% of 430 people who were instead given a 0.9% sodium chloride placebo.
“Because the disease progression to overt pneumonia takes several days, with the peak incidence occurring after 7 days of ventilation, a therapeutic window of opportunity exists to hinder the infectious process early on,” say Stephan Ehrmann, from the University of Tours in France, and colleagues.
The team hypothesized that once-daily nebulization with amikacin for a 3-day period would take advantage of that window.
As reported in The New England Journal of Medicine, the study participants included 292 women and 555 men aged an average of 61.5 years. A total of 78% of the cohort were receiving systemic antibiotics at the time of randomization to amikacin or placebo.
Ventilator-associated pneumonia occurred a median of 10 days from randomization in the amikacin group and 9 days in the placebo group, report Ehrmann and colleagues. They also found that significantly fewer of the amikacin group experienced ventilator-associated conditions, such as worsening oxygenation, compared with their placebo-treated counterparts, at 33% versus 40% and a hazard ratio of 0.79.
Overall, 1.7% of patients receiving amikacin experienced a serious adverse event – such as obstruction of the tracheal tube or bronchospasm – compared with 0.9% of those who received placebo. Furthermore, an acute kidney injury developed in 4% of the amikacin group versus 8% of the placebo group, which equates to a significant 53% reduction in risk with the antibiotic.
“In our trial, the choice of a 3-day preventive therapy course represented a compromise between efficacy and feasibility on the basis of previous experience with inhaled amikacin and other forms of preventive antibiotic therapy in the ICU,” remark Ehrmann et al.
“The enrollment of patients after at least 3 days of invasive mechanical ventilation may have enabled amikacin to act sufficiently early to control the tracheobronchial spread of bacteria before pneumonia occurred, with a majority of patients being extubated a few days after the end of the intervention and thus no longer at risk for ventilator-associated pneumonia,” they conclude.
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