Inhaled amikacin lowers incidence of ventilator-associated pneumonia
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Key takeaways:
- Ventilator-associated pneumonia occurred less frequently in patients who received inhaled amikacin vs. placebo.
- Fewer infection-related ventilator-associated complications took place with amikacin.
Fewer critically ill adults who received inhaled amikacin vs. placebo for 3 days developed ventilator-associated pneumonia by day 28, according to results published in The New England Journal of Medicine.
“The reduction in ventilator-associated pneumonia (VAP) incidence was very large [at a] more than 30% relative reduction. This means one-third of pneumonia episodes can be prevented,” Stephan Ehrmann, MD, PhD, professor at Centre Hospitalier Régional et Universitaire de Tours, told Healio.
In a multicenter, double-blind, randomized, controlled superiority trial, Ehrmann and colleagues assessed 847 critically ill adults on invasive mechanical ventilation for no less than 72 hours to determine whether inhaled amikacin can prevent VAP for 28 days.
Around 80% of patients assigned to receive amikacin (n = 417) or placebo (n = 430) underwent the full 3-day treatment course, making for a total of 337 patients in the inhaled amikacin group (20 mg per kilogram of ideal body weight once daily) and 355 patients in the placebo group.
Researchers found that more patients who received placebo experienced an episode of VAP by day 28 than patients who received amikacin (n = 95; 22% vs. n = 62; 15%), with a difference of 1.5 days (95% CI, 0.6-2.5) in restricted mean survival time to VAP between the two groups.
Among those who developed VAP, the median time to the first episode following randomization was comparable between the amikacin and placebo groups (10 days vs. 9 days).
Similar to the incidence of ventilator-associated pneumonia, fewer patients who received amikacin had a ventilator-associated condition vs. patients who received placebo (n = 137; 33% vs. n = 170; 40%; HR = 0.79; 95% CI, 0.64-0.99).
Researchers also found that fewer patients from the amikacin group experienced an infection-related ventilator-associated complication vs. patients from the placebo group (n = 74; 18% vs. n = 111; 26%; HR = 0.66; 95% CI, 0.5-0.89).
Patients in the amikacin group also had fewer days with one or more administrations of a systemic antibiotic per 1,000 ICU days (570 days vs. 589 days; RR = 0.97; 95% CI, 0.92-1.01) and fewer antibiotic days, which captures the total number of systemic antibiotic treatments received each day, per 1,000 ICU days (887 days vs. 968 days; RR = 0.92; 95% CI, 0.81-1.03) compared with the placebo group.
Among both groups, slightly more patients from the placebo group died in the ICU (n = 112; 26% vs. amikacin, n = 99; 24%; HR = 0.89; 95% CI, 0.68-1.17), according to researchers.
Researchers observed the lower incidence of VAP associated with amikacin persisted among those with tracheobronchial colonization at randomization (n = 185; amikacin, 20% vs. placebo, 27%), and tracheobronchitis at randomization (n = 104; amikacin, 32%; placebo, 33%).
Notably, a few more patients from the amikacin group vs. the placebo group experienced a trial-related serious adverse effect (n = 7; 1.7% vs. n = 4; 0.9%), including four patients who had increased resistance of the expiratory limb filter.
Further, researchers found that an acute kidney injury occurred in 24 patients from the placebo group, compared with only 11 patients from the amikacin group.
When reflecting on the impact of all these findings for the everyday clinician, Ehrmann told Healio that implementation is easy.
“Patient selection is very simple as identifying patients ventilated more than 3 days is straightforward,” he said. “As nebulization appeared very safe, implementation in everyday practice is very simple for clinicians.”
Ehrmann added, “This study validates in large the concept of targeting directly the lung of intubated patients with inhaled anti-infective medications, [which] opens up the way for evaluating inhaled anti-infective therapies beyond antibiotics such as biotherapies with very interesting perspectives for patients.”