Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents.
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 (MIC(50), 0.016 microg/ml; MIC(90), 0.03 microg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. beta-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 microg/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.
Kosowska-Shick
Klaudia
K
Department of Pathology, Hershey Medical Center, PA 17033, USA.
Credito
Kim
K
Pankuch
Glenn A
GA
Lin
Gengrong
G
Bozdogan
Bülent
B
McGhee
Pamela
P
Dewasse
Bonifacio
B
Choi
Dong-Rack
DR
Ryu
Jei Man
JM
Appelbaum
Peter C
PC
D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology; D002444:Cefuroxime / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology*; D000077734:Gatifloxacin; D000077735:Gemifloxacin; D005798:Genes, Bacterial; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D000077266:Moxifloxacin; D009287:Naphthyridines / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D009287:Naphthyridines; D011804:Quinolines; D002939:Ciprofloxacin; D064704:Levofloxacin; D019980:Amoxicillin-Potassium Clavulanate Combination; D017963:Azithromycin; D015242:Ofloxacin; D000077734:Gatifloxacin; C480202:zabofloxacin; D002444:Cefuroxime; D000077735:Gemifloxacin; D000077266:Moxifloxacin