A-61827 (A-60969), a new fluoronaphthyridine with activity against both aerobic and anaerobic bacteria.
A-61827 (A-60969 is the hydrochloric salt of A-61827) is a new aryl-fluoronaphthyridine which is active against aerobic and anaerobic bacteria. The MICs of A-61827 for 90% of strains (MIC90) of staphylococci and streptococci were less than or equal to 1 microgram/ml and were generally 1 to 4 twofold dilutions less than those of ciprofloxacin for these bacteria. The MIC90S of A-61827 for members of the family Enterobacteriaceae and Pseudomonas aeruginosa were also less than or equal to 1 microgram/ml. Ciprofloxacin was 1 to 3 twofold dilutions more active than A-61827 against these gram-negative bacteria. Neisseria gonorrhoeae, Campylobacter jejuni, and Haemophilus influenzae were susceptible to less than 0.06 microgram of A-61827 per ml. The MIC90 of A-61827 for Legionella pneumophila was 0.25 microgram/ml. A-61827 was as potent or 1 to 2 twofold dilutions more potent than ciprofloxacin against these organisms. The MIC90 of A-61827 for all anaerobic bacteria was less than or equal to 4 micrograms/ml compared with less than or equal to 32 micrograms/ml for ciprofloxacin. In mouse protection tests, A-61827 was as active as ciprofloxacin against Escherichia coli, P. aeruginosa, and Salmonella typhimurium and 5 to 10 times more active than ciprofloxacin against Staphylococcus aureus and Streptococcus pyogenes. A-61827 was as active as ciprofloxacin against P. aeruginosa in a mouse pyelonephritis model and more active than ciprofloxacin and metronidazole in a mouse Bacteroides fragilis abscess model. After oral administration of 100 mg/kg to mice, the peak concentrations of A-61827 and ciprofloxacin in serum were 2.3 and 2.4 micrograms/ml and the half-lives in serum were 3.9 and 1.2 h, respectively.
Fernandes
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Anti-Infective Research Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Chu
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Swanson
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Ramer
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Hanson
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Bower
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Stamm
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Hardy
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D000038:Abscess / Q000188:drug therapy; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001420:Bacteria, Aerobic / Q000187:drug effects*; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D001442:Bacteroides Infections / Q000188:drug therapy; D002118:Calcium / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy; D011704:Pyelonephritis / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; C055185:tosufloxacin; D008274:Magnesium; D002118:Calcium