Resistance to quinolones is only due to mutations. The mechanism and the range of quinolones involved, depend on the locus of the chromosomal mutation e.g. a mutation in the gyr A locus is associated with resistance due to changes in the gyrase. Using high inocula in vitro, varying, but relatively low mutation rates of resistance to fluoroquinolones have been found (10(-6)-10(-12). In vitro transfers of bacterial strains in increasing concentrations of quinolones yield parallel increases of the MIC's of most quinolones; however, the MIC's of the most active quinolones like ciprofloxacin usually remain below concentrations achievable in vivo. Exceptions are MIC's for Pseudomonas aeruginosa and staphylococci. Combined resistance to quinolones and other antibiotics was observed after in vitro transfers as well as in mutants (10(-6)-10(-8) isolated from a high inoculum. Changes in the outer membrane proteins have been found in these mutants. Clinical resistance to fluoroquinolones is rare except in Pseudomonas aeruginosa and staphylococci.