In vitro activity of AT-4140 against quinolone- and methicillin-resistant Staphylococcus aureus.

Eighty-nine clinical isolates of Staphylococcus aureus that were resistant to both ciprofloxacin (MIC, greater than or equal to 3.13 micrograms/ml) and methicillin (MIC, greater than or equal to 12.5 micrograms/ml) were divided into two groups with respect to their susceptibilities to AT-4140. Most isolates that were moderately resistant to ciprofloxacin (MICs, 3.13 to 12.5 micrograms/ml) or ofloxacin (MICs, 0.78 to 6.25 micrograms/ml) were susceptible to AT-4140 (MICs, 0.05 to 0.2 microgram/ml). Most isolates that were highly resistant to ciprofloxacin (MIC, greater than or equal to 25 micrograms/ml) or ofloxacin (MIC, greater than or equal to 12.5 micrograms/ml) were resistant to AT-4140 (MICs, 3.13 to 25 micrograms/ml). The appearance of spontaneous single-step, quinolone-resistant mutants of S. aureus P-20, a methicillin-resistant isolate, was more frequent than was that of S. aureus 209P JC-1, a susceptible laboratory strain. Spontaneous single-step, quinolone-resistant mutants of P-20 were not selected by AT-4140, and those selected by existing fluoroquinolones were susceptible to AT-4140. Spontaneous double-step, quinolone-resistant mutants of P-20 were selected by various fluoroquinolones. All second-step mutants selected by AT-4140 or ofloxacin from P-20-C, a spontaneous single-step mutant of P-20 selected by ciprofloxacin, were resistant to all the quinolones. All second-step mutants selected by nonfloxacin were resistant to all existing fluoroquinolones but were less resistant to AT-4140. There was a close resemblance between the resistance profiles of spontaneous quinolone-resistant mutants and those of clinically isolated quinolone- and methicillin-resistant S. aureus.