But, what if the incidence of ventilator-associated pneumonia could be reduced with preventive inhaled antibiotics?
That was the question addressed in an investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial from French researchers.
Critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours were assigned to receive inhaled amikacin at a dosage of 20 mg/kg of ideal body weight once daily or to receive a placebo for 3 days. The primary outcome was defined as a first episode of ventilator-associated pneumonia during the 28 days of follow-up, while safety also was assessed.
For the study published in the New England Journal of Medicine, 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All of the three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group.
The results indicated that at 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% CI, 0.6-2.5; P = .004). The researchers also reported that 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, 0.50-0.89).
Trial-related serious adverse effects were seen in seven patients (1.7%) in the amikacin group and four patients (0.9%) in the placebo group.
“Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up,” according to the study, which was funded by the French Ministry of Health.
The estimated incidence of ventilator-associated pneumonia varies from two to 30 episodes per 1,000 days of mechanical ventilation, based on definition, screening processes, and patient types. According to the report, the disease develops in 5% to 40% of intubated, critically ill patients because microaspirations around the tracheal-tube cuff and the formation of biofilm lead to progressive bacterial spread in the tracheobronchial tree—ultimately leading to pneumonia.
“Ventilator-associated pneumonia is a disease with an attributable mortality of up to 13% and contributes to increased systemic antibiotic consumption, duration of mechanical ventilation and ICU lengths of stay, and costs,” the authors wrote. “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.”
Efforts to control ventilator-associated pneumonia have been going on for decades and include reduced sedation and weaning protocols, patient positioning, management of the tracheal tube cuff, and oral care. Still, the incidence and burden of ventilator-associated pneumonia remains “unacceptably high,” the researchers wrote.
“Inhaled antibiotic therapy enables delivery of very high antibiotic concentrations to the tracheobronchial tree, lung parenchyma, and tracheal-tube biofilm,” they added. The researchers’ hypothesis was that a 3-day course of inhaled amikacin initiated after the third day of invasive mechanical ventilation might reduce the incidence of ventilator-associated pneumonia.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
