In Vitro Selection of Escherichia coli Mutants with Decreased Susceptibility to Norfloxacin

In 10 clinical isolates of Escherichia coli the frequency of spontaneous mutation to high levels of resistance to nalidixic acid was greater than 300-fold higher than that to norfloxacin. Norfloxacin resistant mutants could not be detected (mutation frequency: less than 10(-12). However, nalidixic acid resistant mutants of E. coli developed decreased susceptibility to norfloxacin at a rate of approximately 10(-9). Mutants with decreased susceptibility to norfloxacin could also be obtained when the same clinical isolates of E. coli were exposed to norfloxacin in 2 steps. However, mutants with MIC values greater than 8 micrograms/ml for norfloxacin were never obtained even after repeated exposure. Widespread use of cinoxacin or nalidixic acid may select resistant strains and reduce the efficacy of norfloxacin and other 4-quinolones.