Pharmacodynamics of once- versus twice-daily dosing of nebulized amikacin in an in vitro Hollow-Fiber Infection Model against 3 clinical isolates of Pseudomonas aeruginosa

This study aims to compare the bacterial killing of once-versus twice-daily nebulized amikacin against Pseudomonas aeruginosa and to determine the optimal duration of therapy. Three clinical P. aeruginosa isolates (amikacin MICs 2, 8, and 64 mg/L) were exposed to simulated epithelial lining fluid exposures of nebulized amikacin with dosing regimens of 400 mg and 800 mg once-or twice-daily up to 7-days using the in vitro hollow -fiber infection model. Quantitative cultures were performed. Simulated amikacin dosing regimens of 400 mg twice-daily and 800 mg once-daily achieved >2-log reduction in the bacterial burden within the first 24-hours of therapy for all isolates tested. No dosing regimen suppressed the emergence of amikacin resistance. No difference in bacterial killing or regrowth was observed between 3-and 7-days of amikacin. Amikacin doses of 800 mg once-daily for up to 3-days may be considered for future clinical trials. (c) 2021 Elsevier Inc. All rights reserved.