title: Activity of E-3846, a new fluoroquinolone, in vitro and in experimental cystitis and pyelonephritis in rats.
abstract: The in vitro antibacterial activity of E-3846, a new fluoroquinolone carboxylic acid derivative with a pyrrol ring substituent at position 7, was evaluated in comparison with norfloxacin and ciprofloxacin. E-3846 was more active than the reference quinolones against Staphylococcus species, including methicillin-resistant strains. E-3846 was similar to ciprofloxacin and more active than norfloxacin against Streptococcus (Enterococcus) faecalis. In general, E-3846 was more active than norfloxacin against members of the family Enterobacteriaceae, but less active than ciprofloxacin. For Pseudomonas aeruginosa, the MICs giving 90% inhibition for E-3846, norfloxacin, and ciprofloxacin were 2, 1, and 0.25 micrograms/ml, respectively. The activity of E-3846 increased at acid pH; in contrast, acid pH caused a pronounced decrease in the activity of norfloxacin and ciprofloxacin. In vivo, E-3846 demonstrated excellent therapeutic efficacy in treating experimental S. faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa cystitis and pyelonephritis in rats.
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents; D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D002939:Ciprofloxacin / Q000494:pharmacology; D003556:Cystitis / Q000188:drug therapy*; D004195:Disease Models, Animal; D004755:Enterobacteriaceae / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D024841:Fluoroquinolones; D006863:Hydrogen-Ion Concentration; D007710:Klebsiella Infections / Q000188:drug therapy; D009643:Norfloxacin / Q000494:pharmacology; D011512:Proteus Infections / Q000188:drug therapy; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011704:Pyelonephritis / Q000188:drug therapy*; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D015363:Quinolones; D051381:Rats; D011919:Rats, Inbred Strains; D013210:Staphylococcus / Q000187:drug effects; D013290:Streptococcal Infections / Q000188:drug therapy; D013291:Streptococcus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D000892:Anti-Infective Agents, Urinary; D024841:Fluoroquinolones; D011804:Quinolines; D015363:Quinolones; C056492:6-fluoro-1-cyclopropyl-1,4-dihydro-4-oxo-7-(pyrrol-1-yl)quinoline-3-carboxylic acid; D002939:Ciprofloxacin; D009643:Norfloxacin