BACTERIAL-RESISTANCE TO LB20304, A NEW FLUOROQUINOLONE ANTIBIOTIC

In vitro studies were conducted to determine the frequency rate of spo ntaneous resistance to LB20304 and to determine whether cross-resistan ce to other antimicrobial agents develops. In eight strains of bacteri a, the frequency of mutation to LB20304 at the concentrations of four and eight times the minimal inhibitory concentration (MIC) ranged from less than 4.0 x 10(-10) to 2.2 x 10(-8). These results were similar t o those found for other new fluoroquinolones. The development of stepw ise resistance was determined by repeated subculture in broth in the p resence of increasing concentration of the compounds. Exposure of bact eria 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, St reptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa. H owever, those strains selected after repeated exposure were well withi n the susceptibility range for LB20304 except for Pseudomonas aerugino sa. The resistant isolates selected with LB20304 showed cross-resistan ce when tested against ciprofloxacin and vice versa.