In vitro evaluation of ABT-719, a novel DNA gyrase inhibitor

ABT-719 (A-86719.1) is the first compound of a new class of novel DNA gyrase inhibitors, the 2-pyridones, with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. ABT-719 was more active than ciprofloxacin, sparfloxacin, and clinafloxacin against gram-positive bacteria. ABT-719 was particularly active against Staphylococcus aureus (MIC at which 90% of the isolates were inhibited [MIC90] = 0.015 micrograms/ml) and Streptococcus pneumoniae (MIC90 = 0.03 micrograms/ml). ABT-719 was also the most active of the compounds tested against ciprofloxacin-resistant S. aureus isolates, with an MIC90 of 0.25 micrograms/ml, compared with 64 micrograms/ml for ciprofloxacin. Against gram-negative organisms, ABT-719 was as active as or slightly more active than ciprofloxacin and was the most active compound against ciprofloxacin-resistant Pseudomonas aeruginosa (MIC90 = 2.0 micrograms/ml). ABT-719 was also the most active compound against both gram-positive and gram-negative anaerobes, with MIC90s ranging from 0.12 to 0.25 micrograms/ml.