Activity of new quinolones against ciprofloxacin-resistant staphylococci

Because of the development of newer fluoroquinolones with improved activity against gram-positive organisms, we elected to compare the inhibitory properties of ofloxacin, temafloxacin, sparfloxacin, PD131628, PD127391, and WIN57273 against 105 ciprofloxacin-resistant staphylococci. Based on comparison of MICs for 90% of the organisms (MIC90s), WIN57273 was the most active agent against oxacillin-resistant Staphylococcus aureus; the MIC90 was 0.5 microgram/ml. Against oxacillin-resistant, coagulase-negative staphylococci, PD127391 and WIN57273 were the most active agents; the MIC90 was 0.5 microgram/ml. Against isolates of staphylococci for which ciprofloxacin MICs were greater than or equal to 32 micrograms/ml, WIN57273 and PD127391 still exhibited high activity, inhibiting 100 and 95% of the isolates, respectively, at 2 micrograms/ml. The spontaneous mutation rates for ciprofloxacin-susceptible staphylococci were lowest for ofloxacin. The frequency of spontaneous mutations of ciprofloxacin-resistant staphylococci was low; however, the MICs of PD127391 and WIN57273 for these mutant isolates were greater than 2 micrograms/ml. WIN57273 and PD127391 are two potent new quinolones with high levels of activity against highly ciprofloxacin-resistant staphylococci. There is, however, a major concern of selection of spontaneous mutants resistant to these newer agents.