Amifloxacin and two of its metabolites, N-desmethyl amifloxacin and amifloxacin N-oxide, were evaluated by a microdilution MIC susceptibility test against 500 clinical isolates and compared with ciprofloxacin, lomefloxacin, norfloxacin, aztreonam, and imipenem. Of the Staphylococcus species isolates, 208 were methicillin resistant; the MICs for 78 of the isolates of the family Enterobacteriaceae were 264 pg of cefazolin, ampicillin, piperacillin, and mezlocillin per ml. Based on our results, amifloxacin had activity equivalent to those of norfloxacin and lomefloxacin but was less active than ciprofloxacin. The N-oxide metabolite was the least active; however, for the majority of gram-negative bacteria, N-desmethyl amifloxacin was as active as amifloxacin.The fluoroquinolones exhibit levels of antibacterial activity in vitro and in infections that compare favorably with those of the beta-lactam and aminoglycoside antimicrobial agents (5, 16). Among their advantages is the fact that they are well adsorbed after oral administration. Additionally, the parent compounds may be changed in vivo after oral or parenteral administration and the metabolites produced may have properties different from those of the parent compound (6,8). The disposition and metabolism of amifloxacin have been reported in two animal species, rats and rhesus monkeys (8, 10). In rats, peak concentrations in serum approaching 8 ,ug/ml were obtained, with 40 to 50% of the dose appearing in the urine and the balance appearing in feces. In the urine, 25 to 30% of the dose was unchanged amifloxacin but the primary metabolite by both oral and intravenous dosing routes was piperazinyl-N-oxide (8). The piperazinyl-N-desmethyl metabolite was not observed in rats, but in rhesus monkeys both the piperazinyl-N-desmethyl metabolite and the piperazinyl-N-oxide metabolite were identified (10).In humans, amifloxacin may be metabolized; and the antimicrobial activities of the two primary metabolites would be important in contributing to the overall activity of the compound. This study evaluated the in vitro activities of amifloxacin and two of its identified metabolites, along with those of ciprofloxacin, lomefloxacin, norfloxacin, aztreonam, and imipenem, against clinical bacterial isolates both susceptible and resistant to beta-lactam and aminoglycoside antibiotics.Amifloxacin (WIN 49375) and two putative metabolites, piperazinyl-N-desmethyl amifloxacin and piperazinyl-N-oxide amifloxacin, were provided by Sterling Winthrop Research Institute, Rensselaer, N.Y. (Fig. 1). Broth microdilution panels were prepared by the Senstitre Division of Radiometer/Copenhagen Co. (Lawrence, Mass.). Ciprofloxacin, lomefloxacin, norfloxacin, and the other antimicrobial agents were provided to Sensititre by their manufacturers.Either the Sensititre or our own prepared broth microdilution panels were used to determine MICs, and both MIC methods were performed as recommended by the National * Corresponding author.Committee for Clinical Laboratory Standards (11), with cation-supple...