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

Abstract Objectives To compare the bacterial killing of once- versus twice-daily nebulised amikacin against Pseudomonas aeruginosa and to determine the optimal duration of therapy. Methods Three clinical P. aeruginosa isolates (amikacin MICs 2, 8 and 64 mg/L) were exposed to simulated epithelial lining fluid exposures of nebulised 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. Results 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. Conclusion Amikacin doses of 800 mg once-daily for up to 3-days may be considered for future clinical trials.