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Antimicrobial Agents and Chemotherapy, June 2006, p. 2064-2071, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00153-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antipneumococcal Activity of DW-224a, a New Quinolone, Compared to Those of Eight Other Agents

Klaudia Kosowska-Shick,1 Kim Credito,1 Glenn A. Pankuch,1 Gengrong Lin,1 Bülent Bozdogan,1 Pamela McGhee,1 Bonifacio Dewasse,1 Dong-Rack Choi,2 Jei Man Ryu,2 and Peter C. Appelbaum1*

Department of Medicine, Hershey Medical Center, Hershey, Pennsylvania 17033,1 Dong Wha Pharmaceuticals, Inc., Anyang City, Republic of Korea2

Received 6 February 2006/ Returned for modification 20 March 2006/ Accepted 21 March 2006

DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC50, 0.016 µg/ml; MIC90, 0.03 µg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. ß-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 µg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2x MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days.

* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psu.edu.

Antimicrobial Agents and Chemotherapy, June 2006, p. 2064-2071, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00153-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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