In vitro and in vivo evaluations of A-80556, a new fluoroquinolone.
A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC for 90% of isolates [MIC90], 0.12 microgram/ml, relative to fluoroquinolone-susceptible strains) and Streptococcus pneumoniae (MIC90, 0.12 microgram/ml). A-80556 was also the most active of the quinolones tested against ciprofloxacin-resistant S. aureus, with an MIC90 of 4.0 micrograms/ml; that of ciprofloxacin was > 128 micrograms/ml. However, the significance of this activity is not known. A-80556 was slightly less active against Escherichia coli (MIC90, 0.06 microgram/ml) and other enteric organisms than ciprofloxacin (MIC90 for E. coli, < or = 0.03 microgram/ml). A-80556 was slightly less active against Pseudomonas aeruginosa (MIC90, 4.0 micrograms/ml) than ciprofloxacin (MIC90, 2.0 micrograms/ml) and more active against Acinetobacter spp. (respective MIC90s, 0.12 and 0.5 microgram/ml). A-80556 was also the most active compound against anaerobes. Against Bacteroides fragilis, the MIC90 of A-80556 was 2.0 micrograms/ml; that of ciprofloxacin was 16 micrograms/ml. The in vivo efficacy of A-80556 in experimental models with both gram-positive and gram-negative infections was consistent with the in vitro activity and pharmacokinetics and oral absorption in mice.
Clement
J J
JJ
Abbott Laboratories, Abbott Park, Illinois 60064-3500.
Tanaka
S K
SK
Alder
J
J
Vojtko
C
C
Beyer
J
J
Hensey
D
D
Ramer
N
N
McDaniel
D
D
Chu
D T
DT
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001421:Bacteria, Anaerobic / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D004352:Drug Resistance, Microbial; D005260:Female; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C088878:A 80556