Inhaled amikacin for severe Gram-negative pulmonary infections in the intensive care unit: current status and future prospects

Abstract

Recently, the use of nebulized antibiotics in the intensive care unit, in particular amikacin, has been the subject of much discussion, owing to unconvincing results from the latest randomized clinical trials. Here, we examine and reappraise the evidence in favor and against this therapeutic strategy; we then discuss the potential factors that might have played a role in the negative findings of recent clinical trials. Also, we call attention to several factors that are seldom considered by study developers and regulatory agencies, to promote translational research in this field and improve the design of future randomized clinical trials.

Keywords: Amikacin; Gram-negative bacteria; Pseudomonas aeruginosa; Ventilator-associated pneumonia.

Fig. 1

Bronchoscopic evaluation of mechanically ventilated Large White Landrace pigs challenged by Pseudomonas aeruginosa. a Main right upper bronchus, prior to bacterial challenge; of note no abnormalities can be found. b After 24 h from inoculation of 15 mL of 10⁷ colony forming units of P. aeruginosa, the distal portion of the right middle bronchus is copiously filled with purulent secretions with a reduction of the distal bronchi by more than 60%. c Main right medium bronchus, prior to bacterial challenge, with no abnormalities. d After 24 h from inoculation of 15 mL of 10⁷ colony forming units of P. aeruginosa, the bronchial mucosa is highly hyperemic and retained purulent secretions are evident throughout the bronchus, almost completely obstructing distal bronchi