Bacterial Resistance to LB20304, a New Fluoroquinolone Antibiotic

In vitro studies were conducted to dertermine the frequency rate of spontaneous resistance to LB20304 and to dertermine whether cross-resistance to other antimicrobial agents develops. In eight strains of bacteria, the frequency of mutation to LB20304 at the concentrations of four and eight times the minimal inhibitory concentration(MIC) ranaged from less than 4.0 ${\times}$ $10^{-10}$ to 2.2 $\{times}$ $10^{-10}$ . These results were similar to those founf for other new fluoroquinolones. THe development of stepwise resistance was determined by repeated subculture in broth in the presence of increasing concentration of the compounds. Exposure of bacteria to increasing concentrations of LB20304 resulted in the selection of organisms with higher MICs. There were 4- to 128-fold increases in the MIC of LB20304 for bacterial strains of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa. However, those strains selected after repeated exposure were well within the susceptibility range for LB20304 except for Pseudomonas aeruginosa. The resistant isolates selected with LB20304 showed cross-resistance when tested against ciprofloxacin and vice versa.