DR-3355, the S-(-)-isomer of ofloxacin, was generally twice as potent as ofloxacin against a variety of gram-positive and gram-negative pathogens, and its action was bactericidal. The compound was characterized by having the highest level of activity against staphylococci, Bacteroides fragilis, and Peptococcus spp. of the fluorinated quinolones tested, including ofloxacin, ciprofloxacin, fleroxacin, and NY-198. The activity of DR-3355 was not affected by different media, inoculum size, or human serum, but decreased under acidic conditions at pH 5.0 or in human urine.During the past decade, the development of fluorinated quinolones such as norfloxacin (6), ofloxacin (10), ciprofloxacin (12), fleroxacin (3), and NY-198 (4) has been aimed mainly at enhancing activity against gram-negative and gram-positive pathogens. Among these compounds, ofloxacin (10) is characterized chemically by a tricyclic structure with a methyl group at the C-3 position in the oxazine ring, thus providing an asymmetric center at this position (Fig. 1). In the course of studies on the structure-activity relationships between stereochemistry and activity, two optically active isomers of ofloxacin, i.e., DR-3355 [S-(-)-ofloxacin] and DR-3354 [R-(+)-ofloxacin], were prepared successfully by use of their optically resolved synthetic intermediates ( Fig. 1) (2). A preliminary study of the spectrum of activity of these isomers against selected laboratory strains revealed that DR-3355 was 8 to 128 times more potent than DR-3354 and approximately twice as active as ofloxacin (2). In this paper we describe the in vitro activity of DR-3355, relative to other fluorinated quinolones, against a large number of clinical isolates.
MATERIALS AND METHODSCompounds. DR-3355 and ofloxacin were synthesized at the Research Institute, Daiichi Seiyaku Co., Ltd., Tokyo, Japan, as were ciprofloxacin, fleroxacin, and NY-198. Methicillin sodium (Banyu Pharmaceutical Co., Ltd., Tokyo, Japan) and clindamycin phosphate (Japan Upjohn Ltd., Tokyo, Japan) were commercial products.Organisms Ofloxacin: R = -CH3