Background
It is unclear whether preventive inhaled antibiotics can reduce the incidence of ventilator-associated pneumonia.
Methods
In this multicenter, double-blind, randomized, controlled, investigator-initiated superiority trial, we assigned critically ill adults who had been on invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram. of body weight once a day or receive placebo for 3 days.
The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was evaluated.
Results
A total of 850 patients were randomized and 847 were included in the analyzes (417 assigned to the amikacin group and 430 to the placebo group). The three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group.
At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted median survival time with respect to ventilator-associated pneumonia). to ventilator, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004).
An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89).
Serious trial-related adverse events were observed in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group.
Conclusions Among patients who had been mechanically ventilated for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia over 28 days of follow-up. |
(Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640. opens in a new tab; EUDRA Clinical Trials number, 2016-001054-17. opens in a new tab.)
