Amikacin protects mechanically ventilated patients from ventilator-associated pneumonia

Usually occurring 48 hours or more after mechanical breathing via a tracheostomy or endotracheal tube, ventilator-associated pneumonia (VAP) is linked to increased antibiotic use, resistance, longer stays in the intensive care unit (ICU), and higher fatality rates. After seven days of ventilation, the peak incidence appears, providing a treatment window for reducing the likelihood of VAP. Nine studies with moderate sample sizes were meta-analyzed to show that VAP prophylaxis was effective. Inhaled amikacin's preventive ability to reduce VAP incidence in critically sick patients ventilated for at least 72 hours was examined in the AMIKINHAL study, which compared it to a placebo to prevent VAP. During a 28-day follow-up, the multicenter, double-blind, randomised study with 847 individuals showed a substantial decrease in the incidence of VAP in the amikacin group as compared to the placebo group. Furthermore, the amikacin group had significantly fewer ventilator-associated problems due to infections. One weakness of the study was that it lacked the capacity to evaluate the outcomes of death and length of ICU stay. According to the experiment, individuals with VAP may benefit from a further three-day regimen of inhaled amikacin.

850 patients from 19 intensive care units in France were included in the trial; 417 patients received amikacin after three patients withdrew their permission, and 430 received a placebo. Nebulized sodium chloride or amikacin was given to patients at random, with participants and treating doctors kept in the dark. 78% of patients were taking systemic antibiotics at the time of randomization. Three hundred and thirty-seven patients (81%) in the amikacin group and three hundred and thirty-five patients (83%) in the sodium chloride group completed all three planned nebulizations. The development of VAP post-nebulization was the main result, while the duration of stay, mortality, median number of days on mechanical ventilation, events related to the ventilator, and days of antibiotic use were important secondary outcomes. After 28 days, 62 patients (15%) in the amikacin group and 95 patients (22%) in the placebo group had ventilator-associated pneumonia (difference in limited mean survival time to ventilator-associated pneumonia, 1.5 days; 95% Confidence Interval [CI], 0.6 to 2.5; p=0.004) that had developed. Additionally, 111 patients (26%) in the placebo group and 74 patients (18%) in the amikacin group had a ventilator-associated problem attributable to an infection (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Four patients (0.9%) in the placebo group and seven patients (1.7%) in the amikacin group had trial-related major side events. With regard to the possible preventative use of inhaled antibiotics in critically sick patients, this investigator-initiated study offers crucial information.

The researchers  concluded  that the use of inhaled amikacin reduced ventilator-associated pneumonia (VAP) in patients on mechanical ventilation for more than three days.Amikacin inhalation was linked to a decrease in the incidence of VAP throughout a 28-day period of observation.

Reference –

Ehrmann, S., Barbier, F., Demiselle, J., Quenot, J.-P., Herbrecht, J.-E., Roux, D., Lacherade, J.-C., Landais, M., Seguin, P., Schnell, D., Veinstein, A., Gouin, P., Lasocki, S., Lu, Q., Beduneau, G., Ferrandiere, M., Plantefève, G., Dahyot-Fizelier, C., Chebib, N., … Tavernier, E. (2023). Inhaled amikacin to prevent ventilator-associated pneumonia. The New England Journal of Medicine, 389(22), 2052–2062. https://doi.org/10.1056/nejmoa2310307