The in vitro and in vivo activities of DW286, a novel fluoronaphthyridone with potent antibacterial activity, were compared with those of ciprofloxacin, gemifloxacin, sparfloxacin, and trovafloxacin. Against gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis, the in vitro activity of DW286 was stronger than that of any other reference antibiotic. Against gram-negative bacteria, the activity of DW286 was similar to those of trovafloxacin and gemifloxacin but was weaker than that of ciprofloxacin. In a mouse systemic infection caused by three S. aureus strains, including methicillin-resistant S. aureus and quinolone-resistant S. aureus (QRSA), DW286 demonstrated the most potent activity, as found in vitro. Specially, DW286 is >8-fold more active against QRSA than the other fluoroquinolones. And the 50% protective doses for DW286 were correspondent with the in vitro activities.The quinolones have evolved from agents used solely for the treatment of urinary tract infections to molecules with potent activity against a wide spectrum of significant bacterial pathogens. Progressive modifications in their molecular configurations have improved both the spectrum and potency of their in vitro activities (2). These compounds have been successfully used in clinics for a decade. The targets in fluoroquinolone research during the last few years include improving the pharmacokinetic properties, increasing the activity against grampositive cocci and anaerobes and against fluoroquinolone-resistant strains, and improving activity against nonfermentative gram-negative species (1,4,5,6). In addition, the increasing pathogen resistance to antimicrobial agents is a cause of concern. This increase in the resistance to fluoroquinolone emphasizes the importance of the continued development of new structural candidates (3,4,5,6,7). The use of newer fluoroquinolone derivatives will potentially contribute to decreasing the spread of resistance to other antimicrobial agents by reducing the selective pressure on other antibiotic groups (5). New candidates have been developed in an attempt to help improve this situation. DW286, 7-[3-(aminomethyl)-4-(methoxyimino)-3-methyltetrahydro-1H-1-pyrrolyl]-1-cyclopropyl-6-fluoro-4-oxo-1, 4-dihydro [1,8]naphthyridine-3-carboxylic acid hydrochloric acid salt, is a novel fluoronaphthyridone antibacterial agent that was synthesized for this purpose (Fig. 1). In this study, we determined the in vitro activity of DW286 in several groups of clinical isolates and compared it with those of ciprofloxacin, gemifloxacin, sparfloxacin, and trovafloxacin. We also compared the in vivo protective efficacy of DW286 with those of the fluoroquinolones against a systemic infection in mice.The studied compounds were obtained as follows: DW286, ciprofloxacin, sparfloxacin, and gemifloxacin were synthesized at the R & D Center, Dong Wha Pharmaceutical Company, Anyang City, Korea. Trovafloxacin was provided by Pfizer Pharmaceuticals, New York,...

There was no significant difference in antibiotic effects between moxifloxacin and levofloxacin on most bacterial strains, except for Serratia marcescens. On the other hand, levofloxacin seemed to be safer than moxifloxacin in HCECs.