Journal of Antimicrobial Chemotherapy (2001) 48, 29-36
© 2001 The British Society for Antimicrobial Chemotherapy
Activity of non-fluorinated quinolones (NFQs) against quinolone-resistant Escherichia coli and Streptococcus pneumoniae
Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA
The newly developed 8-methoxy, non-fluorinated quinolones (NFQs) were studied to elucidate their enzyme inhibitory activity against wild-type and mutant GyrA (Ser-83
Trp) forms of Escherichia coli DNA gyrase. Using a DNA supercoiling inhibition assay, the NFQs were found to inhibit 50% (IC50) of the E. coli DNA gyrase activity in the 1.6–3.2 mg/L concentration range and were comparable to ciprofloxacin. However, against the GyrA (Ser-83Trp) mutant, the NFQs were ~16-fold more potent than ciprofloxacin. Antibacterial potency of the NFQs was investigated using clinical isolates of E. coli and penicillin-resistant Streptococcus pneumoniae (PRSP), including strains with reduced susceptibility to quinolones. Against 20 uncharacterized clinical isolates of E. coli, the MIC90s of the NFQs were in the 0.125–0.25 mg/L range while those of ciprofloxacin, trovafloxacin, gatifloxacin and clinafloxacin were in the 0.016–0.125 mg/L range. Against clinical isolates with characterized mutations in gyrA and parC, PGE9262932, an NFQ, was two- to eight-fold more potent than ciprofloxacin. Against 23 clinical isolates of PRSP, the NFQs (MIC90 0.031–0.125 mg/L) were more potent than ciprofloxacin, trovafloxacin, and gatifloxacin (MIC90 0.25–2.0 mg/L), and at least as potent as clinafloxacin (MIC90 0.125 mg/L). Against S. pneumoniae strains with gyrA and parC mutations, the NFQs (MIC 0.125–1.0 mg/L) were more potent than ciprofloxacin, trovafloxacin and gatifloxacin (MIC 4–32 mg/L), and comparable to clinafloxacin (MIC 0.5–1 mg/L).
* Corresponding author. Tel: +1-513-622-3928; Fax: +1-513-622-0085; E-mail: roychoudhury.s{at}pg.com
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