In vitro antibacterial activities of PD 131628, a new 1,8-naphthyridine anti-infective agent

Abstract

PD 131628 is a new aminopyrrolidine-substituted fluorocyclopropyl naphthyridine quinolone which possesses high in vitro activity against a wide spectrum of bacterial species. The MICs for .90% of strains were 0.125 to 0.25 ,ug/ml for staphylococci, Streptococcus pyogenes, and S. pneumoniae; 0.5 ,ug/ml for S. agalactiae and Enterococcus faecalis; 0.125 jug/ml for members of the family Enterobacteriaceae and Acinetobacter spp.; 0.5 ,Lg/mI for Pseudomonas aeruginosa; and <0.03 ,ug/ml for Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Neisseria gonorrhoeae. In these in vitro comparisons with ciprofloxacin, PD 131628 is more active against gram-positive organisms, approximately equivalent against gram-negative organisms, and, like most other quinolones, relatively inactive against gram-negative anaerobes. In most instances, the in vitro potency of PD 131628 exceeded those of widely used compounds:

Susceptibilities of 123 Xanthomonas maltophilia strains to clinafloxacin, PD 131628, PD 138312, PD 140248, ciprofloxacin, and ofloxacin

“…Activity was greatest in strains for which ciprofloxacin MICs were s2.0 ,ug/ml. Clinafloxacin and PD 131628 are two new experimental fluoroquinolones with expanded activity against gram-positive and gram-negative organisms, including members of the family Enterobacteriaceae, Streptococcus pneumoniae, and some anaerobes (5,6,9,12,16). This study confirms the increased activity against X. maltophilia reported by other workers (5,6,8,16).…”

“…Available quinolones such as ciprofloxacin and ofloxacin are marginally active, with MICs for susceptible isolates clustering around the breakpoint (1,4,9,(12)(13)(14). Clinafloxacin (CI-960, PD 127391) and PD 131628 (the active component of the prodrug CI-990) are two new fluoroquinolones with improved activity against gram-positive cocci, gramnegative nonfermenters, and anaerobes (5,6,8,9,12,16). This study compared the activities of clinafloxacin, PD 131628, two other experimental broad-spectrum fluoroquinolones (PD 138312 and PD 140248) (2, 7), ciprofloxacin, and ofloxacin against 123 clinical isolates of X maltophilia.…”

“…Clinafloxacin and PD 131628 are two new experimental fluoroquinolones with expanded activity against gram-positive and gram-negative organisms, including members of the family Enterobacteriaceae, Streptococcus pneumoniae, and some anaerobes (5,6,9,12,16). This study confirms the increased activity against X. maltophilia reported by other workers (5,6,8,16). In view of the inherent resistance of X. maltophilia strains to most classes of antimicrobial agents (3,10,11,13,17), clinafloxacin and PD 131628 may represent additional drugs which may be useful in treatment of infections caused by these organisms.…”

Comparative activity of ciprofloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, CI-990, and WIN 57273 against anaerobic bacteria

“…Consequently, industry has attempted to synthesize new compounds with improved antianaerobic activity (5). We evaluated the activities of seven fluoroquinolone compounds against 290 recent clinical anaerobic isolates and three American Type Culture Collection (ATCC) strains.…”

CI-990 (PD 131112): A New Quinolone Prodrug

“…The remaining fluoroquinolones had little activity against this organism. Pharmacokinetic studies have shown that CI-990's active drug PD 131628 is released rapidly upon oral or parenteral administration in experimental animals and has excellent absorption and distribution properties [19].…”