Dissociated resistance among fluoroquinolones

Abstract

A panel of 190 clinical isolates of staphylococci, enterococci, Streptococcus pneumoniae, members of the family Enterobacteriaceae, and nonfermentative gram-negative bacilli were examined by agar dilution tests for susceptibility to five quinolones and six nonquinolone agents. Members of the family Enterobacteriaceae and staphylococci were divided into subgroups according to their ciprofloxacin susceptibilities and were analyzed for cross-resistance to OPC-17116, ofloxacin, and temafloxacin. Although the MICs of all quinolones increased with increasing ciprofloxacin resistance, the MICs of OPC-17116, ofloxacin, and temafloxacin tended to increase less than those of ciprofloxacin, indicating that these agents were less affected by the mechanisms of quinolone resistance. An exception to this was the activity of OPC-17116 against highly ciprofloxacin-resistant staphylococci (MIC, > or = 8 micrograms/ml). Some of these staphylococci were equally resistant to OPC-17116, while others were fourfold more susceptible to ciprofloxacin than to OPC-17116. This indicated that in some strains OPC-17116 was more affected than ciprofloxacin by certain mechanisms responsible for high-level resistance. This was paralleled in single-step mutational studies in which 7 of 19 staphylococcal mutants exhibited large decreases in susceptibility to OPC-17116 (128- to 256-fold) but only modest decreases in susceptibility (4- to 16-fold) to the other quinolones. Such mutants were selected only from strains moderately resistant to ciprofloxacin (MIC, > or = 1 microgram/ml). This heterogeneity in the resistance of staphylococci to fluoroquinolones has not been seen previously and suggests that certain mechanisms of resistance in staphylococci affect OPC-17116 to a much greater extent than other quinolones.