Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines

SB-265805 (formerly LB20304) is a novel C-7 pyrrolidine-substituted naphthy ridone that has a broad spectrum of activity, especially against Gram-posit ive cocci. SB-265805 activity was compared with ciprofloxacin, grepafloxaci n, moxifloxacin, sparfloxacin, and penicillin against 599 Streptococcus spp . isolated recently from more than 30 medical centers in North, and South A merica. These included 70 isolates with decreased susceptibility to recentl y released fluoroquinolones (levofloxacin MIC, greater than or equal to 4 m u g/mL). All strains were tested by reference microdilution methods in lyse d house blood-supplemented Mueller-Hinton broth. Sixteen percent of 148 bet a-haemolytic streptococci (strains of gr. B and C) were not susceptible to penicillin, whereas 38% and 42% of viridans group streptococci and Streptoc occus pneumoniae were resistant to penicillin, respectively. SB-265805 pote ncy against 301 pneumococci (MIC90, 0.06 mu g/mL) was four-fold more active than moxifloxacin and was greater than or equal to eightfold more potent t han other quinolones. Against beta-haemolytic streptococci, SE-265805 and m oxifloxacin were the most active (MIC90, 0.06 and 0.25 mu g/mL, respectivel y), whereas sparfloxacin, grepafloxacin, and ciprofloxacin (MIC90, 0.5-1 mu g/mL) were less potent. SB-265805 MICs versus viridans group streptococci (MIC90, 0.12 mu g/mL) were fourfold lower than sparfloxacin or grepafloxaci n, and twofold more active than moxifloxacin. A nine-laboratory quality con trol (QC) protocol conforming to NCCLS M23-T3 guidelines demonstrated a mod al SB-265805 MIC of 0.016 mu g/mL for S. pneumoniae ATCC 49619 (proposed QC range, 0.008 to 0.03 mu g/mL). The SB-265805 disk (5-mu g) QC range was 28 -34 mm (97.3% of qualifying results). In general, SB-265805 in vitro activi ty against Streptococcus species was superior to sparfloxacin, grepafloxaci n, and moxifloxacin and markedly greater than ciprofloxacin. This degree of antimicrobial potency warrants further investigation of this newer drug fo r its potential human clinical application against streptococcal infections . (C) 1999 Elsevier Science Inc.