The in-vitro activity of CP 99, 219, a new naphthyridone antimicrobial agent: a comparison with fluoroquinolone agents

Abstract

The in-vitro activity of a new fluoroquinolone, CP 99,219 was compared with that of ciprofloxacin, DU 6859, sparfloxacin and levofloxacin. CP 99,219 showed generally similar in-vitro activity to the other compounds tested against the Enterobacteriaceae (MIC90 of all agents < 0.5 mg/L except Morganella morganii). It was found to be more active than ciprofloxacin, sparfloxacin and levofloxacin against the strains of Acinetobacter calcoaceticus tested (MIC90 1 mg/L). CP 99,219 was found to be four-fold more active against strains of Stenotrophomonas maltophilia than ciprofloxacin (MIC90 1 and 8 mg/L, respectively). Haemophilus influenzae and Neisseria spp. were highly susceptible to all the agents tested. CP 99,219 was more active than ciprofloxacin, sparfloxacin and levofloxacin against Gram-positive organisms, but less active than DU 6859. The enhanced anti-Gram-positive activity of CP 99,219 was most marked against the nine strains of methicillin-resistant Staphylococcus aureus tested. The MIC90 of CP 99,219 of these strains was 1.0 mg/L compared with 64 mg/L for ciprofloxacin. Against Bacteroides fragilis, CP 99,219 (MIC90 0.25 mg/L) and DU 6859 (MIC90 0.03 mg/L) were more active than the other quinolones. Chlamydia spp. were susceptible to < or = 0.12 mg/L of CP 99,219. Mycobacterial strains tested were less susceptible to CP 99,219 than to ciprofloxacin. The protein binding of CP 99,219 was 87.9% at 1 mg/L.

Plasmid curing effect of trovafloxacin

“…Trovafloxacin (CP‐99,219), a new fluoroquinolone containing the C‐7 ring moiety 7‐(3‐azabicyclo[3.1.0]hexyl) on N‐1 o , p ‐difluorophenyl naphthyridone [9], was chosen for clinical development on the basis of its long half‐life and broad spectrum. Compared to ciprofloxacin, trovafloxacin has a markedly improved activity against Gram‐positive cocci and anaerobes, while maintaining the good activity of ciprofloxacin against Gram‐negative pathogens [10–16].…”

Fluoroquinolone antibacterials: SAR, mechanism of action, resistance, and clinical aspects

“…5), and trovafloxacin (33, Table VII) have the most potent activity against these species, with MIC,,s of 50.25 &mL for S. pneumoniue reported. [222][223][224][225][226][227] Values for enterococci vary with these agents, although MIC,,s are usually between 0.12 and 2 pg/mL. Unfortunately, some vancomycin-resistant enterococci are also resistant to these new fluoroquinolones, with reported MICs above 4 pg/mL.228-230 While new antimicrobials are clearly needed against multi-resistant enterococci, the new fluoroquinolones may not have sufficient potency to be effective in vivo against the majority of these isolates.…”

Science, medicine, and the future: The development of new antimicrobial agents

“…Recently, fluoroquinolones have appeared and are soon to be marketed (such as trovafloxacin which is active against anaerobic bacteria2) or will be available in 2-3 years (such as SmithKline Beecham's SB265805, which has enhanced activity against Gram positive bacteria3). The β lactam structure has been such a fruitful source of compounds in the past with the penicillins, cephalosporins, and carbapenems (among others) being so useful.…”