The Drug-Specific Propensity Regarding the Acquisition of Fluoroquinolone Resistance in : An in vitro Challenge and DNA Mutation Analysis.

OBJECTIVE

Many fluoroquinolones, such as ciprofloxacin, are used clinically. We investigated the relationship between resistance acquisition and exposure duration in each drug through the exposure of fluoroquinolone to clinical isolates in vitro.

METHODS

Eleven clinical isolates were exposed to each fluoroquinolone, ie, ciprofloxacin, levofloxacin, sitafloxacin, garenoxacin, and lascufloxacin, with the concentration of the mutant selection window for 5 days; these procedures were repeated 5-times. In addition, the DNA sequence in the quinolone-resistance determining region (QRDR) and the expression level in the drug efflux pump were analyzed to determine the resistance mechanism.

RESULTS

Although resistant strains were not detected after 5 to 10 days of exposure to fluoroquinolone, after 25 days of exposure to ciprofloxacin and levofloxacin, 100% and 45% of isolates acquired resistance, respectively. Due to 25 days of exposure to sitafloxacin, garenoxacin, and lascufloxacin, MIC measurement was elevated 2- to 4096-fold for those of the parental strain, and the cross-resistance rate to levofloxacin was 72%, 54%, and 27%, respectively. In strains with high fluoroquinolone resistance, overexpression was observed in addition to QRDR mutation.

CONCLUSION

In our findings, fluoroquinolone resistance was not observed in the strain after 5- to 10-days of exposure. However, resistance acquisition was detected frequently after 15- to 25-days of exposure. Among fluoroquinolones, lascufloxacn had the least impact on the resistance acquisition in .