In vitro activity of garenoxacin tested against a worldwide collection of ciprofloxacin-susceptible and ciprofloxacin-resistant Enterobacteriaceae strains (1999–2004)

Garenoxacin is a novel des-F(6)-quinolone with a chemical structure that lacks the C6 position fluorine and has a unique difluoromethoxy substitution at position C8. This study evaluated the in vitro activity of garenoxacin tested against a large collection of Enterobacteriaceae collected worldwide. The bacterial isolates were consecutively collected from more than 70 medical centers from bloodstream, respiratory, urinary tract, and skin and soft tissue infections. The isolates were tested against garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and many other oral and parenteral antimicrobial agents. All isolates were susceptibility tested by broth microdilution methods according to the Clinical and Laboratory Standards Institute (CLSI) guidelines and interpretative criteria. A garenoxacin-susceptible breakpoint of ≤2 μg/mL was applied for comparison purposes only. The fluoroquinolones were the most active oral compounds with overall susceptibility rates of 87.5% to 90.0%. Garenoxacin showed in vitro activity comparable with that of ciprofloxacin and the other fluoroquinolones against Escherichia coli (MIC50, ≤0.03 μg/mL; 87.3% susceptible), Klebsiella spp. (MIC50, 0.12 μg/mL; 90.4–94.5% susceptible), Enterobacter spp. (MIC50, 0.12 μg/mL; 85.6–86.5% susceptible), Salmonella spp. (MIC50, 0.06 μg/mL; 99.7% susceptible), and Shigella spp. (MIC50, ≤0.03 μg/mL; 99.9% susceptible), which accounted for 87.0% of the Enterobacteriaceae strains tested. Garenoxacin was highly active against ciprofloxacin-susceptible strains (98.1% susceptibility), whereas ciprofloxacin-resistant strains were generally resistant to all other fluoroquinolones and also showed high rates of resistance to other orally administered antimicrobials. In conclusion, garenoxacin in vitro activity was similar to that of currently marketed fluoroquinolones and superior to other orally administered antimicrobial agents (cephalosporins, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole) when tested against more than 45 000 globally collected Enterobacteriaceae.