Testing the premise that inhalation of antibiotics reduces the incidence of ventilator-associated pneumonia, French and Chinese investigators show clinical benefits of a 3-day course of inhaled amikacin. The antibiotic was administered to patients after at least 3 days of invasive mechanical ventilation, enabling the “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,” the authors write.
Critically ill adults were randomized to inhaled amikacin 20 mg/kg once daily or placebo for 3 days in the investigator-initiated, multicenter, double-blind, superiority trial. Based on safety outcomes and a primary outcome of a first episode of ventilator-associated pneumonia during 28 days of follow-up, the authors found: “A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All 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 mean survival time to ventilator-associated pneumonia, 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 in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group.”