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  • Title: Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines.
    Author: Johnson DM, Jones RN, Erwin ME.
    Journal: Diagn Microbiol Infect Dis; 1999 Feb; 33(2):87-91. PubMed ID: 10091031.
    Abstract:
    SB-265805 (formerly LB20304) is a novel C-7 pyrrolidine-substituted naphthyridone that has a broad spectrum of activity, especially against Gram-positive cocci. SB-265805 activity was compared with ciprofloxacin, grepafloxacin, moxifloxacin, sparfloxacin, and penicillin against 599 Streptococcus spp. isolated recently from more than 30 medical centers in North and South America. These included 70 isolates with decreased susceptibility to recently released fluoroquinolones (levofloxacin MIC, > or = 4 micrograms/mL). All strains were tested by reference microdilution methods in lysed horse blood-supplemented Mueller-Hinton broth. Sixteen percent of 148 beta-haemolytic streptococci (strains of gr. B and C) were not susceptible to penicillin, whereas 38% and 42% of viridans group streptococci and Streptococcus pneumoniae were resistant to penicillin, respectively. SB-265805 potency against 301 pneumococci (MIC90, 0.06 microgram/mL) was fourfold more active than moxifloxacin and was > or = eightfold more potent than other quinolones. Against beta-haemolytic streptococci, SB-265805 and moxifloxacin were the most active (MIC90, 0.06 and 0.25 microgram/mL, respectively), whereas sparfloxacin, grepafloxacin, and ciprofloxacin (MIC90, 0.5-1 microgram/mL) were less potent. SB-265805 MICs versus viridans group streptococci (MIC90, 0.12 microgram/mL) were fourfold lower than sparfloxacin or grepafloxacin, and twofold more active than moxifloxacin. A nine-laboratory quality control (QC) protocol conforming to NCCLS M23-T3 guidelines demonstrated a modal SB-265805 MIC of 0.016 microgram/mL for S. pneumoniae ATCC 49619 (proposed QC range, 0.008 to 0.03 microgram/mL). The SB-265805 disk (5-microgram) QC range was 28-34 mm (97.3% of qualifying results). In general, SB-265805 in vitro activity against Streptococcus species was superior to sparfloxacin, grepafloxacin, and moxifloxacin and markedly greater than ciprofloxacin. This degree of antimicrobial potency warrants further investigation of this newer drug for its potential human clinical application against streptococcal infections.
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