Mutation rates to 4-quinolone resistance.

The sensitivity of Staph. aureus, Staph. warneri, Pseudomonas aeruginosa, Strep. pneumoneae and Strep. faecalis to eleven 4-quinolone antibacterials was compared by determining their minimum inhibitory concentrations on nutrient agar. In all cases where the minimum inhibitory concentration was less than 10 micrograms/ml then the frequency at which 4-quinolone-resistant mutants arose was estimated using each drug at 5, 10 and 20 times its minimum inhibitory concentration. It was found with all five bacterial species tested that ciprofloxacin and ofloxacin were the most potent antibacterial and that no mutants could be detected in 10(12) bacteria for either drug with Staph. warneri, Strep. pneumoneae and Strep. faecalis. On the other hand, mutants of Pseudomonas aeruginosa resistant to both 5 and 10 times (but not 20 times) the minimum inhibitory concentrations of ofloxacin and ciprofloxacin were detected at similar frequencies in the 10(12) bacteria tested. With Staph. aureus, mutants resisting 5 times (but not 10 or 20 times) the minimum inhibitory concentrations of ofloxacin and ciprofloxacin were detected in the 10(12) bacteria tested at similar frequencies. However, all mutants resistant to ciprofloxacin retained the ability to produce coagulase while the majority of ofloxacin-resistant mutants had lost their ability to produce coagulase. Hence clear evidence for pathogenicity loss was observed with ofloxacin but not with ciprofloxacin.