Pharmacodynamics of amikacin in vitro and in mouse thigh and lung infections

A variety of in-vitro and animal studies were performed to define the pharmacodynamic characteristics of amikacin against Gram-negative bacilli and to determine the impact of the dosing regimen on therapeutic efficacy. Mice with impaired renal function were included in these studies to more closely simulate in animals the pharmacokinetics of amikacin observed in humans. Amikacin exhibited concentration-dependent killing and produced prolonged postantibiotic effects both in vitro and in vivo. In mice with renal impairment, the efficacy of once-daily dosing of amikacin was similar to or greater than that observed with 6- and 12-hour dosing regimens. The antibacterial activity of amikacin in these mice correlated best with the AUC and peak serum concentration. The time course of antimicrobial activity demonstrated in these studies for amikacin against Gram-negative bacilli would support once-daily dosing in humans.