Rapid selection of organisms with increasing resistance on subinhibitory concentrations of norfloxacin in agar

Serial passage of Pseudomonas aeruginosa ATCC 27853 or Escherichia coli ATCC 25922 on agar with subinhibitory concentrations of norfloxacin rapidly produced isolates with minimal inhibitory concentrations (MICs) of norfloxacin up to 512-fold higher than that for the original strain. Although MICs of seven unrelated antibiotics were unchanged, increasing MICs occurred in parallel with norfloxacin, cinoxacin, and nalidixic acid regardless of which of these three organic acids was used to select for increased resistance. P. aeruginosa with a norfloxacin MIC of greater than 256 micrograms/ml could be selected; however, E. coli with MICs greater than the clinically achievable level of 16 micrograms/ml could not be produced.