Multiple mutations conferring ciprofloxacin resistance in Staphylococcus aureus demonstrate long-term stability in an antibiotic-free environment

Two unrelated strains of Staphylococcus aureus, one with a single mutation in grlA, the other with multiple mutations in gyrA, gyrB, grlA, grlB, norA and the norA promoter region, encoding low-level and high-level ciprofloxac in resistance, respectively, were studied. The characterized mutations in t hese genes were conserved when both strains were passaged for at least 500 generations in an antibiotic-free environment. New, rapidly stabilized muta tions and higher MICs were detected for strains passaged in sub-MIC ciprofl oxacin concentrations. The seeming irreversibility of quinolone resistance may affect the long-term success of this drug class.