Comparative antimicrobial spectrum and activity of BMS284756 (T-3811, a desfluoroquinolone) tested against 656 Enterobacteriaceae, including preliminary in vitro susceptibility test comparisons and development.
BMS284756 (T-3811), a novel des-F(6)-quinolone, was evaluated using isolates of Enterobacteriaceae from the SENTRY Antimicrobial Surveillance Program tested by Etest (AB BIODISK, Solna, Sweden), reference broth microdilution and disk diffusion (5-microg) methods. Ciprofloxacin, levofloxacin, gemifloxacin and gatifloxacin were also tested by broth microdilution as comparator antimicrobial agents within the same drug class. The 656 isolate collection included species from the genera Citrobacter, Enterobacter, Escherichia, Hafnia, Klebsiella, Morganella, Pantoea, Proteus, Providencia, Salmonella, and Serratia. BMS284756 was slightly less active than comparison fluoroquinolones against these isolates (MIC(90), 4 mg/l versus 0.06-2 mg/l). However, at a proposed susceptible breakpoint of < or =4 mg/l, 90.7% of the isolates processed were susceptible to BMS284756, demonstrating an equivalent spectrum of activity to all other agents except gemifloxacin (86.6%). In general, isolates requiring >4 mg/l of BMS284756 for inhibition of growth were also less susceptible to the comparators suggesting cross-resistance is common between des-F(6)- and fluoro-quinolones. Excellent correlation was observed between broth microdilution MIC results and 5-microg disk zone diameters (r=0.94), and between broth microdilution dilution and Etest MIC values (r=0.96). In conclusion, BMS284756 has an activity and spectrum similar to contemporary fluoroquinolones and in vitro test methods (NCCLS, Etest) appear accurate and reproducible